Synergistic therapeutic effect of arsenic trioxide and radiotherapy in BALB/C nude mice bearing nasopharyngeal carcinoma xenografts
It has been shown that arsenic trioxide (ATO) induced apoptosis in human nasopharyngeal carcinoma cells and inhibited the growth of nasopharyngeal carcinoma xenografts (NPCX) in nude mice. Aim: The present study was designed to determine whether ATO at the non-toxic dose level could potentiate the t...
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Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України
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Xie, L.X. Lin, X.H. Li, D.R. Chen, J.Y. Hong, C.Q. Du, C.W. 2018-06-19T09:33:45Z 2018-06-19T09:33:45Z 2007 Synergistic therapeutic effect of arsenic trioxide and radiotherapy in BALB/C nude mice bearing nasopharyngeal carcinoma xenografts / L.X. Xie, X.H. Lin, D.R. Li, J.Y. Chen, C.Q. Hong, C.W. Du // Experimental Oncology. — 2007. — Т. 29, № 1. — С. 45-48. — Бібліогр.: 18 назв. — англ. 1812-9269 https://nasplib.isofts.kiev.ua/handle/123456789/138563 It has been shown that arsenic trioxide (ATO) induced apoptosis in human nasopharyngeal carcinoma cells and inhibited the growth of nasopharyngeal carcinoma xenografts (NPCX) in nude mice. Aim: The present study was designed to determine whether ATO at the non-toxic dose level could potentiate the therapeutic effectiveness of radiation therapy in nasopharyngeal carcinoma, using a BALB/C nude mouse xenograft model. Methods: The mice bearing NPCX were treated with radiation alone (2, 4, and 6 Gy), ATO alone (4 mg/kg/day x 6 days), and ATO plus radiation at the same dosage levels. Time of tumor growth delay (defined as the time necessary for the tumor to grow four-fold of its initial volume after, compared with untreated tumors) and toxic effects were determined. Results: The low dose ATO alone has no pronounced effects on tumor growth delay compared to untreated control. However, compared with radiation alone, the combined regimen delayed the tumor growth by 2–10 days and had no significant toxic effects such as the liver function damage. Conclusions: Combination of ATO at non-toxic dose level and radiation has synergistic effects on tumor growth inhibition in vivo and is well tolerated. Установлено, что триоксид мышьяка (ТОМ) индуцирует апоптоз в клетках карциномы носоглотки человека и ингибирует рост ксенографта карциномы носоглотки у атимических мышей. Цель работы — установить терапевтическую эффективность радиотерапии в комбинации ТОМ в нетоксичной дозе мышам линии BALB/ с ксенографтом карциномы носоглотки. Методы: животные с ксенографтом карциномы носоглотки получали либо только радиотерапию (2, 4 и 6 Гр) или ТОМ (4 мг/кг/день в течение 6 дней), или их комбинацию в тех же режимах и дозах. Задержку роста опухоли определяли как различие во времени, необходимом для достижения опухолью 4-кратного объема по сравнению с начальным объемом в опытной группе versus такового в контрольной группе. Результаты: введение ТОМ в низкой дозе не оказывало выраженного влияния на рост опухоли по сравнению с показателями в контрольной группе, а в комбинации с облучением приводило к задержке роста опухоли на 2–12 сут по сравнению с показателями у животных, получавших только лучевую терапию при отсутствии выраженных побочных эффектов. Выводы: комбинация ТОМ в нетоксической дозе и лучевой терапии приводит к ингибированию роста опухоли in vivo и не вызывает побочных эффектов. Ключевые слова: триоксид мышьяка, радиотерапия, ксенографт карциномы носоглотки. This work was supported by the Shantou University Research and Development grant (L03002), the Traditional Chinese Medicine Research grant of Guangdong Province (102053), China. en Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України Experimental Oncology Original contributions Synergistic therapeutic effect of arsenic trioxide and radiotherapy in BALB/C nude mice bearing nasopharyngeal carcinoma xenografts Синергичный терапевтический эффект триоксида мышьяка и радиотерапии у мышей линии BALB/C с ксенографтами карциномы носоглотки Article published earlier |
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Digital Library of Periodicals of National Academy of Sciences of Ukraine |
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| title |
Synergistic therapeutic effect of arsenic trioxide and radiotherapy in BALB/C nude mice bearing nasopharyngeal carcinoma xenografts |
| spellingShingle |
Synergistic therapeutic effect of arsenic trioxide and radiotherapy in BALB/C nude mice bearing nasopharyngeal carcinoma xenografts Xie, L.X. Lin, X.H. Li, D.R. Chen, J.Y. Hong, C.Q. Du, C.W. Original contributions |
| title_short |
Synergistic therapeutic effect of arsenic trioxide and radiotherapy in BALB/C nude mice bearing nasopharyngeal carcinoma xenografts |
| title_full |
Synergistic therapeutic effect of arsenic trioxide and radiotherapy in BALB/C nude mice bearing nasopharyngeal carcinoma xenografts |
| title_fullStr |
Synergistic therapeutic effect of arsenic trioxide and radiotherapy in BALB/C nude mice bearing nasopharyngeal carcinoma xenografts |
| title_full_unstemmed |
Synergistic therapeutic effect of arsenic trioxide and radiotherapy in BALB/C nude mice bearing nasopharyngeal carcinoma xenografts |
| title_sort |
synergistic therapeutic effect of arsenic trioxide and radiotherapy in balb/c nude mice bearing nasopharyngeal carcinoma xenografts |
| author |
Xie, L.X. Lin, X.H. Li, D.R. Chen, J.Y. Hong, C.Q. Du, C.W. |
| author_facet |
Xie, L.X. Lin, X.H. Li, D.R. Chen, J.Y. Hong, C.Q. Du, C.W. |
| topic |
Original contributions |
| topic_facet |
Original contributions |
| publishDate |
2007 |
| language |
English |
| container_title |
Experimental Oncology |
| publisher |
Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України |
| format |
Article |
| title_alt |
Синергичный терапевтический эффект триоксида мышьяка и радиотерапии у мышей линии BALB/C с ксенографтами карциномы носоглотки |
| description |
It has been shown that arsenic trioxide (ATO) induced apoptosis in human nasopharyngeal carcinoma cells and inhibited the growth of nasopharyngeal carcinoma xenografts (NPCX) in nude mice. Aim: The present study was designed to determine whether ATO at the non-toxic dose level could potentiate the therapeutic effectiveness of radiation therapy in nasopharyngeal carcinoma, using a BALB/C nude mouse xenograft model. Methods: The mice bearing NPCX were treated with radiation alone (2, 4, and 6 Gy), ATO alone (4 mg/kg/day x 6 days), and ATO plus radiation at the same dosage levels. Time of tumor growth delay (defined as the time necessary for the tumor to grow four-fold of its initial volume after, compared with untreated tumors) and toxic effects were determined. Results: The low dose ATO alone has no pronounced effects on tumor growth delay compared to untreated control. However, compared with radiation alone, the combined regimen delayed the tumor growth by 2–10 days and had no significant toxic effects such as the liver function damage. Conclusions: Combination of ATO at non-toxic dose level and radiation has synergistic effects on tumor growth inhibition in vivo and is well tolerated.
Установлено, что триоксид мышьяка (ТОМ) индуцирует апоптоз в клетках карциномы носоглотки человека и ингибирует
рост ксенографта карциномы носоглотки у атимических мышей. Цель работы — установить терапевтическую эффективность
радиотерапии в комбинации ТОМ в нетоксичной дозе мышам линии BALB/ с ксенографтом карциномы носоглотки.
Методы: животные с ксенографтом карциномы носоглотки получали либо только радиотерапию (2, 4 и 6 Гр) или ТОМ
(4 мг/кг/день в течение 6 дней), или их комбинацию в тех же режимах и дозах. Задержку роста опухоли определяли как
различие во времени, необходимом для достижения опухолью 4-кратного объема по сравнению с начальным объемом в
опытной группе versus такового в контрольной группе. Результаты: введение ТОМ в низкой дозе не оказывало выраженного
влияния на рост опухоли по сравнению с показателями в контрольной группе, а в комбинации с облучением приводило
к задержке роста опухоли на 2–12 сут по сравнению с показателями у животных, получавших только лучевую терапию
при отсутствии выраженных побочных эффектов. Выводы: комбинация ТОМ в нетоксической дозе и лучевой терапии
приводит к ингибированию роста опухоли in vivo и не вызывает побочных эффектов.
Ключевые слова: триоксид мышьяка, радиотерапия, ксенографт карциномы носоглотки.
|
| issn |
1812-9269 |
| url |
https://nasplib.isofts.kiev.ua/handle/123456789/138563 |
| citation_txt |
Synergistic therapeutic effect of arsenic trioxide and radiotherapy in BALB/C nude mice bearing nasopharyngeal carcinoma xenografts / L.X. Xie, X.H. Lin, D.R. Li, J.Y. Chen, C.Q. Hong, C.W. Du // Experimental Oncology. — 2007. — Т. 29, № 1. — С. 45-48. — Бібліогр.: 18 назв. — англ. |
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| fulltext |
Experimental Oncology ���� ������� ����� ��arc��� ������ ������� ����� ��arc��� ���arc��� ���� �� ��
It �as been well known t�at radiation t�erapy �RT��
is one of t�e major effective treatments for nasop�a-
ryngeal carcinoma. However�� due to t�e �ig� dose of
radiation�� patients frequently suffer from toxic effects��
suc� as xerostomia�� �earing loss�� �ypomnesia�� dys-
p�agia [1]�� neck stiffness [�]�� and nasal synec�ia [3].
T�ere is an urgent need for novel approac�es to im-
proving response of cancer cells to radiation t�erapy.
Unfortunately�� effective non-toxic radiosensitizers for
clinical use are �ard to find.
Arsenic trioxide �ATO�� �as been reported as an ef-
fective agent in t�e treatment of patients wit� leukemia
[��6]. Recently�� several studies �ave been focused on
t�e antitumor effects of ATO on solid tumors [���11].
It �as been reported t�at ATO en�anced radiation
response in glioma [��� �]�� cervical cancer [1�]�� �ead
and neck squamous cell carcinomas [11]. In our
previous studies�� we demonstrated several potential
mec�anisms by w�ic� ATO reduced t�e invasive and
metastatic properties of nasop�aryngeal carcinoma
cells�� including G�/� arrest�� up-regulation of p�3
and Bax expression�� and down-regulation of Bcl-�
expression [1��� 13]. In addition�� we found t�at ATO
en�anced radiosensitivity of nasop�aryngeal carci-
noma cells in vitro [13]. T�us�� it is reasonable to de-
termine w�et�er ATO can increase radiation response
of nasop�aryngeal carcinoma in vivo. T�e aims of our
present study are to determine t�e t�erapeutic effects
of ATO�� RT�� and combination of t�e bot� treatments on
nasop�aryngeal carcinoma in vivo�� to detect t�e toxic
effects of t�e combined treatment�� if any�� and to evalu-
ate t�e potential benefits for future clinical use.
MATERIALS AND METHODS
Test compound and reagents. ATO was pur-
c�ased from Harbin-Eda P�armaceutical Co. Ltd�� C�i-
na. Ot�er reagents are t�e �ig�est grade available.
Animal model and treatment. BALB/C mice��
���� weeks of age and weig�ing 1���� g�� were ob-
tained from t�e Experimental Animal Center of Sun
Yat-Sen �edical University �Guang Z�ou�� C�ina��. T�e
current study was approved by t�e Et�ic Committee
of Cancer Hospital�� S�antou University.
T�e mice were raised under SPF �specific pat�ogen
free�� condition. Human nasop�aryngeal carcinoma
cell line�� CSNET-1�� was used in t�e experiment. It is a
poorly differentiated squamous cell carcinoma�� usually
maintained in a frozen state�� and �as been proven to be
transplantable in severe combined immunodeficiency
�SCID�� mice [1�]. Before experiment�� 1�6 exponentially
growing cancer cells were inoculated subcutaneously
into t�e back of several Balb/c nude mice. W�en tumors
reac� approximately � mm in lengt� diameter�� t�ey were
obtained by surgical resection�� minced wit� scissors
into fragments of about 1 mm in diameter and t�en
implanted subcutaneously into t�e armpit of BALB/C
mice. W�en tumors were palpable �~ � mm in lengt�
diameter���� mice were randomly divided into several
groups: one untreated control�� t�ree groups treated wit�
radiation alone �RT���� one ATO alone �ATO���� and t�ree
groups wit� ATO plus radiation �ATO + RT��. RT and ATO +
RT groups were treated wit� single radiation of ��� ��� and
6 Gy�� respectively. T�ere were � mice in eac� group.
ATO �� mg/kg per day�� was administered i. p. for
6 days. In t�e combined treratment�� after t�e last ATO
treatment�� local irradiation of ��� � or 6 Gy was delivered
SYNERGISTIC THERAPEUTIC EFFECT OF ARSENIC TRIOXIDE
AND RADIOTHERAPY IN BALB/C NUDE MICE BEARING
NASOPHARYNGEAL CARCINOMA XENOGRAFTS
L.X. Xie1, X.H. Lin2, D.R. Li1, *, J.Y. Chen1, C.Q. Hong1, C.W. Du1
1Laboratory of Cancer Research, Tumor Hospital, Shantou University Medical College, Shantou, China
2Department of Biomedical Engineering, School of Engineering and Applied Science, Washington
University, Saint Louis, USA
It has been shown that arsenic trioxide (ATO) induced apoptosis in human nasopharyngeal carcinoma cells and inhibited the growth
of nasopharyngeal carcinoma xenografts (NPCX) in nude mice. Aim: The present study was designed to determine whether ATO
at the non-toxic dose level could potentiate the therapeutic effectiveness of radiation therapy in nasopharyngeal carcinoma, using
a BALB/C nude mouse xenograft model. Methods: The mice bearing NPCX were treated with radiation alone (2, 4, and 6 Gy),
ATO alone (4 mg/kg/day x 6 days), and ATO plus radiation at the same dosage levels. Time of tumor growth delay (defined as the
time necessary for the tumor to grow four-fold of its initial volume after, compared with untreated tumors) and toxic effects were
determined. Results: The low dose ATO alone has no pronounced effects on tumor growth delay compared to untreated control.
However, compared with radiation alone, the combined regimen delayed the tumor growth by 2–10 days and had no significant toxic
effects such as the liver function damage. Conclusions: Combination of ATO at non-toxic dose level and radiation has synergistic
effects on tumor growth inhibition in vivo and is well tolerated.
Key Words: arsenic trioxide, radiation, nasopharyngeal carcinoma xenografts.
Received: February 7, 2007.
*Correspondence: Fax: +86-754-8560352
E-mail: liderui2007@yahoo.com.cn
Abbreviations used: ALT — alanine aminotransferase; AST — as-
partate aminotransferase; ATO — arsenic trioxide; RT — radiation
therapy.
Exp Oncol �����
���� 1�� �����
�6 Experimental Oncology ���� ������� ����� ��arc���
wit� an X-ray mac�ine �Tape 1T1-V�� Beijing�� C�ina���� ope-
rating at 1�� KV�� 1� mA�� �.� mm Cu-equivalent filter��
wit� a dose rate of 1���.3cGy/min. During irradiation��
unanest�etized mice were placed and fixed in speciallymice were placed and fixed in specially
designed Perspex boxes�� isolated from t�e air�� and t�e and t�e
normal tissue around t�e tumor was s�ielded as muc�
as possible by placing some lead coverings upon t�e
surface of t�e boxes.
Measurement of tumor growth. Tumor size was
measured wit� vernier calipers�� and tumor volume was
calculated by t�e formula a × b�/� �a is t�e maximal dia-
meter�� b is t�e minimal diameter�� [1�]. T�e measure-
ment was performed daily after inoculation of tumor��
and weekly after radiation. Relative tumor volume wasRelative tumor volume was
determined by taking t�e initial volume before radiation
as 1. T�e time needed for a xenograft to reac� �-fold. T�e time needed for a xenograft to reac� �-fold
of its initial volume was defined as TGT�. Time of tumor
growt� delay �TGD�� was t�e TGT� w�en compared wit�
t�e control group�� e. g. TGD of RT group compared wit�
untreated group�� TGD of RT + ATO group compared wit�
RT alone group.
Detection of toxic effect. In all experiments��
mice were monitored daily for signs of toxicity. OnOn
t�e ��t� week after radiation�� w�en t�e relative volume
of tumor in eac� group reac�ed � times of t�e initial
volume�� t�e mice were sacrificed. T�en t�e blood sam-
ples were collected. Examination of serum aspartateaspartate
aminotransferase �AST�� and alanine aminotransferase
�ALT�� levels were performed using an automated bio-
c�emistry mac�ine �Olympus�� Japan�� for evaluation of
t�e toxic effects on liver function. After mice were sac-
rificed�� t�e toxic effects of t�erapy on t�e state of �eart��
lungs�� liver�� kidneys were detected �istologically.
Additional 1� mice were treated using t�e same
regimen as in t�e group treated wit� ATO alone to
evaluate t�e acute toxic effects.
Statistical analysis. T�e results of TGD�� AST�� and
ALT analyses were expressed as t�e mean ± standard
deviation. T�e Student’s t-test was used to determine
t�e significance of t�e differences among t�e treated
groups compared wit� controls. A p- value of < �.��
was considered statistically significant.
RESULTS
Tumor response to the combined treatment of
ATO and radiation. On t�e 1�t� day after t�e implanta-
tion of nasop�aryngeal carcinoma xenograft in mice��
��% of tumors were palpable �> � mm in lengt� diame-
ter��. On t�e �t� week after radiation t�erapy�� or t�e
�3t� day after tumor implantation�� tumors in eac� group
grew more t�an �-fold compared wit� t�at before ra-
diation. T�ere was no obvious c�ange in weig�t�� signs
of life�� activity among various treatment groups.
T�e TGT�’s in t�e ATO alone group and t�e untreated
group were �.� ± �.�� and �.� ± �.�� days�� respectively
�p = �.������ indicating t�at ATO treatment alone �ad no
impact on tumor growt�. In addition�� at t�e dose used
in t�e present study�� ATO �ad no �ost toxicity�� t�erefore
considering t�is dose as a non-toxic dose. However��
compared wit� t�at of RT alone group�� t�e tumor
growt� delay by radiation was significantly en�anced
by ATO in a dose-dependent manner w�en combined
wit� t�e non-toxic doses of ATO. As s�own in Table 1��
w�en t�e relative tumor volume reac�ed ��� t�e tumor
growt� delay from t�e combined treatment wit� ATO
and RT was estimated to be about � �� Gy���� 13 �� Gy����
and �1 days �6 Gy���� respectively�� after t�e effects of
ATO were deducted from t�e results�� significantly
greater t�an t�at from RT alone �p < �.���� �Figure��.
Table 1���� Tumor growth delay in experimental animals treated by RT alone
and combined treatment with ATO and RT
RT dose Tumor growth delay (days)
RT alone ATO + RT p value
2 Gy 1.9 ± 0.6 3.9 ± 1.3 < 0.05
4 Gy 7.6 ± 1.8 13 ± 2.4 < 0.05
6 Gy 11.9 ± 2.9 21.7 ± 4.4 < 0.05
Figure. T�e effects of combined treatment wit� ATO and radiation
on nasop�aryngeal carcinoma xenografts in BALB/C nude mice
Evaluation of AST and ALT. No significant diffe-
rences in t�e levels of AST and ALT between control
group and group wit� combined treatment by RT and ATO
were observed �p > �.������ suggesting t�at t�e combined
treatment was well tolerated in t�e experimental animals
�Table ���.
Table 2�� AST and ALT levels in untreated group of animals and combined
treatment group
Groups Results of liver function test
AST U/L ALT U/L
Untreated
RT + ATO (2 Gy)
RT + ATO (4 Gy)
RT + ATO (6 Gy)
Control for toxic effect
40.1 ± 24.8
37.8 ± 32.4
37.3 ± 34.3
41.3 ± 35.1
47.3 ± 21.4
196.3 ± 45.6
174.7 ± 49.7
169.5 ± 52.3
178.2 ± 40.2
201.2 ± 25.5
There are no significant difference between the treated group and untreated
group (p > 0.5).
�oreover�� no obvious toxic c�anges were found �is-
tologically in liver�� lung�� kidney�� and �eart tissue�� and no
metastases were not found as well. T�ere were no differ-
ences in t�e toxicity among various treatment groups.
DISCUSSION
Some recent studies �ave indicated t�at ATO mig�t
en�ance radiation response in some solid tumors
[���11�� 16]�� and t�e combined treatment wit� ATO and
fractionated radiot�erapy are effective in t�e treat-
ment of relapsed acute promyelocytic leukemia [1��]��
but t�ere are no in vivo data supporting its effect in
nasop�aryngeal carcinoma.
Hig� dose of radiation alone or ATO alone was
required to treat nasop�aryngeal carcinoma effec-
Experimental Oncology ���� ������� ����� ��arc��� ������� ������� ����� ��arc��� ����arc��� ����� ��� ���
tively�� but some pat�ological c�anges in liver and
cardiac tissues were found [1�]. In t�e current study��
TGT� was used to determine t�e treatment effect�� t�us��
t�e radiation doses used in t�e current study s�ould
enable all t�e xenografts to reac� � times of t�eir initial
volumes and s�ould not cause tumor disappearance
after irradiation. T�at is w�y we c�ose relatively low
radiation doses �� Gy�� � Gy�� 6 Gy�� for t�e experiment.
Before t�e drug administration�� we performed several
preliminary experiments to determine t�e dose of
ATO. T�ree doses ���� ���� and 1� mg/kg�� were used��
t�e ATO doses at �� and 1� mg/kg could lead to severe
toxicity including deat�. In contrast�� no mice died at
t�e dose of � mg/kg�� indicating t�at low dose of ATO
caused less toxic effects. �oreover�� ATO alone at t�e
dose of � mg/kg �ad no pronounced antitumor ef-
fect compared wit� t�e untreated controls. T�erefore
t�e combination treatment wit� low dose of ATO may
�ave clinical implication. Our results s�owed t�at t�e
combined treatment wit� ATO and radiation delayed
tumor growt� significantly�� suggesting t�e synergistic
effects between ATO and radiation.
To determine t�e time for tumor growt� delay w�en
t�e relative tumor volume reac�ed � times of t�e initial
tumor size�� t�e data for ATO alone as control was de-
ducted�� t�us t�e in�ibitory effect of tumor growt� by
combined ATO and RT s�owed t�e synergistic effects.
As s�own in Table 1�� TGD of ATO combined wit� RT was
�ig�er t�an t�at of RT alone�� w�ic� was dependent on
t�e dose of radiation. T�ese results �ave demonstrated
en�ancement of radiation response by ATO in naso-
p�aryngeal carcinoma in vivo�� and furt�er confirmed
our previous results in vitro [13].
Considering t�at liver disfunction is a major adverse
event of ATO in clinical treatment of leukemia [1�]�� we
investigated t�e effects of combined treatment wit� ATO
and RT on t�e level of AST and ALT in mice. To our knowl-
edge�� t�is is t�e first report on toxic effects of ATO on
liver function in solid tumor models. We used two groups
of animals for combined treatment�� one was sacrificed
s�ortly after t�e last time of drug administration�� anot�er
one was sacrificed by t�e end of t�e experiments. No
significant difference in t�e levels of AST and ALT was
found among t�e two groups and t�e untreated group��
indicating t�at no obvious liver disfunction was caused
by t�e combined treatment. �oreover�� no significant
toxic effects eit�er by observation of activity�� weig�t or
pat�ological morp�ology�� indicating t�e combination
wit� ATO and RT was a well tolerable treatment.
In conclusion�� low dose of ATO en�ances t�e
response of nasop�aryngeal carcinoma to radia-
tion t�erapy in nude mouse xenograft models w�ic�
provides a basis for future studies wit� t�is combined
regimen in patients wit� nasop�aryngeal carcinoma
ACkNOwLEDGEMENT
T�is work was supported by t�e S�antou University
Researc� and Development grant �L�3������� t�e Tradi-
tional C�inese �edicine Researc� grant of Guangdong
Province �1����3���� C�ina.
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СИНЕРГИЧНЫЙ� �ЕР��Е��ИЧЕС�ИЙ� ���Е�� �РИ��СИ�� �ЕР��Е��ИЧЕС�ИЙ� ���Е�� �РИ��СИ���ЕР��Е��ИЧЕС�ИЙ� ���Е�� �РИ��СИ�� ���Е�� �РИ��СИ�����Е�� �РИ��СИ�� �РИ��СИ���РИ��СИ��
МЫШЬЯ�� И Р��И��ЕР��ИИ �� МЫШЕЙ� �ИНИИ BALB/C И Р��И��ЕР��ИИ �� МЫШЕЙ� �ИНИИ BALB/CИ Р��И��ЕР��ИИ �� МЫШЕЙ� �ИНИИ BALB/C Р��И��ЕР��ИИ �� МЫШЕЙ� �ИНИИ BALB/CР��И��ЕР��ИИ �� МЫШЕЙ� �ИНИИ BALB/C �� МЫШЕЙ� �ИНИИ BALB/C�� МЫШЕЙ� �ИНИИ BALB/C МЫШЕЙ� �ИНИИ BALB/CМЫШЕЙ� �ИНИИ BALB/C �ИНИИ BALB/C�ИНИИ BALB/C BALB/C
С �СЕН�ГР����МИ ��Р�ИН�МЫ Н�С�Г����И �СЕН�ГР����МИ ��Р�ИН�МЫ Н�С�Г����И�СЕН�ГР����МИ ��Р�ИН�МЫ Н�С�Г����И ��Р�ИН�МЫ Н�С�Г����И��Р�ИН�МЫ Н�С�Г����И Н�С�Г����ИН�С�Г����И
Установлено, что триоксид мышьяка (ТОМ) индуцирует апоптоз в клетках карциномы носоглотки человека и ингибирует
рост ксенографта карциномы носоглотки у атимических мышей. Цель работы — установить терапевтическую эффектив-
ность радиотерапии в комбинации ТОМ в нетоксичной дозе мышам линии BALB/C с ксенографтом карциномы носоглотки.BALB/C с ксенографтом карциномы носоглотки./C с ксенографтом карциномы носоглотки.C с ксенографтом карциномы носоглотки. с ксенографтом карциномы носоглотки.
Методы: животные с ксенографтом карциномы носоглотки получали либо только радиотерапию (2, 4 и 6 Гр) или ТОМ
(4 мг/кг/день в течение 6 дней), или их комбинацию в тех же режимах и дозах. �адержку роста опухоли определяли какв течение 6 дней), или их комбинацию в тех же режимах и дозах. �адержку роста опухоли определяли как 6 дней), или их комбинацию в тех же режимах и дозах. �адержку роста опухоли определяли как
различие во времени, необходимом для достижения опухолью 4-кратного объема по сравнению с начальным объемом в
опытной группе versus такового в контрольной группе. Результаты: введение ТОМ в низкой дозе не оказывало выраженного
влияния на рост опухоли по сравнению с показателями в контрольной группе, а в комбинации с облучением приводило
к задержке роста опухоли на 2–12 сут по сравнению с показателями у животных, получавших только лучевую терапию
при отсутствии выраженных побочных эффектов. Выводы: комбинация ТОМ в нетоксической дозе и лучевой терапии
приводит к ингибированию роста опухоли in vivo vivovivo и не вызывает побочных эффектов.
Ключевые слова: триоксид мышьяка, радиотерапия, ксенографт карциномы носоглотки.
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