Metformin plus PIAF combination chemotherapy for hepatocellular carcinoma

Metformin plus PIAF combination chemotherapy for hepatocellular carcinoma

Objectives: Metformin, the most used oral antidiabetic drug for the treatment of type 2 diabetus mellitus, has proved encouraging results when used in the treatment of various types of cancer such as triple-negative breast cancer. Despite compelling evidence of a role of metformin as an anticancer d...

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Veröffentlicht in:Experimental Oncology
Datum:2012
Hauptverfasser: Petrushev, B., Tomuleasa, C., Soritau, O., Aldea, M., Pop, T., Susman, S., Kacso, G., Berindan, I., Irimie, A., Cristea, V.
Format: Artikel
Sprache:English
Veröffentlicht: Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України 2012
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Online Zugang:https://nasplib.isofts.kiev.ua/handle/123456789/138685
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Zitieren:Metformin plus PIAF combination chemotherapy for hepatocellular carcinoma / B. Petrushev, C. Tomuleasa, O. Soritau, M. Aldea, T. Pop, S. Susman, G. Kacso, I. Berindan, A. Irimie, V. Cristea // Experimental Oncology. — 2012. — Т. 34, № 1. — С. 17-24. — Бібліогр.: 35 назв. — англ.

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Digital Library of Periodicals of National Academy of Sciences of Ukraine
id nasplib_isofts_kiev_ua-123456789-138685
record_format dspace
spelling Petrushev, B.
Tomuleasa, C.
Soritau, O.
Aldea, M.
Pop, T.
Susman, S.
Kacso, G.
Berindan, I.
Irimie, A.
Cristea, V.
2018-06-19T11:38:47Z
2018-06-19T11:38:47Z
2012
Metformin plus PIAF combination chemotherapy for hepatocellular carcinoma / B. Petrushev, C. Tomuleasa, O. Soritau, M. Aldea, T. Pop, S. Susman, G. Kacso, I. Berindan, A. Irimie, V. Cristea // Experimental Oncology. — 2012. — Т. 34, № 1. — С. 17-24. — Бібліогр.: 35 назв. — англ.
1812-9269
https://nasplib.isofts.kiev.ua/handle/123456789/138685
Objectives: Metformin, the most used oral antidiabetic drug for the treatment of type 2 diabetus mellitus, has proved encouraging results when used in the treatment of various types of cancer such as triple-negative breast cancer. Despite compelling evidence of a role of metformin as an anticancer drug, the mechanisms by which metformin exerts its oncostatic actions are not fully understood yet. Therefore, we tried to bring new insights by analyzing the anti-neoplastic effect of metformin for hepatocellular carcinoma-derived stem-like cells treated with conventional combination chemotherapy. Methods: Cancer stem-like cells previusly isolated from a hepatocellular carcinoma biopsy were treated with metformin, PIAF chemotherapy regimen and the combination of these two protocols. Measurements of lipid peroxidation, reduced glutathione, fluorescein diacetate and proliferation rates were determined, apart from the autophagy assay and apoptosis determination by chip flow cytometry. Results: Metformin alone and especially metformin in association with PIAF increases oxidative stress within the cells by increasing the levels of lipid peroxids as well as decreasing the levels of reduced glutathione. The MTT cell proliferation assay showed decreased prolife­ration rates for the arm treated with metformin and with the combination of drugs in comparison with the control arm, proving high correlation with the oxidative stress results. The autophagy assay and determination of apoptosis by chip flow cytometry confirmed the results obtained in the previous assays. Conclusion: Metformin could be used in chemotherapy treatments to induce reactive oxygen species and increase the cytostatics effects within the tumor cell. Still, further experiments must be carried out on murine models before we can move on and use this drugs in the adjuvant setting for unresectable primary liver cancer.
This research has never been published before and was financially supported by a research grant of the Iuliu Hatieganu University of Medicine and Pharmacy, granted to Bobe Petrushev — MD. All the experiments were carried out both at the Department of Cancer Immunology, Ion Chiricuta Comprehensive Cancer Center in Cluj Napoca and at the G.I. Core Center at Johns Hopkins University, under the supervision of Ciprian Tomuleasa, MD (Postdoctoral Researcher at The Johns Hopkins University in Baltimore, MD, USA) and Professor Victor Cristea, MD, PhD (Head of Department and Attending physician in Clinical Gastroenterology and Hepatology at the Octavian Fodor Regional Institute of Gastroenterology and Hepatology, Cluj Napoca, Romania).
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Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України
Experimental Oncology
Original contributions
Metformin plus PIAF combination chemotherapy for hepatocellular carcinoma
Article
published earlier
institution Digital Library of Periodicals of National Academy of Sciences of Ukraine
collection DSpace DC
title Metformin plus PIAF combination chemotherapy for hepatocellular carcinoma
spellingShingle Metformin plus PIAF combination chemotherapy for hepatocellular carcinoma
Petrushev, B.
Tomuleasa, C.
Soritau, O.
Aldea, M.
Pop, T.
Susman, S.
Kacso, G.
Berindan, I.
Irimie, A.
Cristea, V.
Original contributions
title_short Metformin plus PIAF combination chemotherapy for hepatocellular carcinoma
title_full Metformin plus PIAF combination chemotherapy for hepatocellular carcinoma
title_fullStr Metformin plus PIAF combination chemotherapy for hepatocellular carcinoma
title_full_unstemmed Metformin plus PIAF combination chemotherapy for hepatocellular carcinoma
title_sort metformin plus piaf combination chemotherapy for hepatocellular carcinoma
author Petrushev, B.
Tomuleasa, C.
Soritau, O.
Aldea, M.
Pop, T.
Susman, S.
Kacso, G.
Berindan, I.
Irimie, A.
Cristea, V.
author_facet Petrushev, B.
Tomuleasa, C.
Soritau, O.
Aldea, M.
Pop, T.
Susman, S.
Kacso, G.
Berindan, I.
Irimie, A.
Cristea, V.
topic Original contributions
topic_facet Original contributions
publishDate 2012
language English
container_title Experimental Oncology
publisher Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України
format Article
description Objectives: Metformin, the most used oral antidiabetic drug for the treatment of type 2 diabetus mellitus, has proved encouraging results when used in the treatment of various types of cancer such as triple-negative breast cancer. Despite compelling evidence of a role of metformin as an anticancer drug, the mechanisms by which metformin exerts its oncostatic actions are not fully understood yet. Therefore, we tried to bring new insights by analyzing the anti-neoplastic effect of metformin for hepatocellular carcinoma-derived stem-like cells treated with conventional combination chemotherapy. Methods: Cancer stem-like cells previusly isolated from a hepatocellular carcinoma biopsy were treated with metformin, PIAF chemotherapy regimen and the combination of these two protocols. Measurements of lipid peroxidation, reduced glutathione, fluorescein diacetate and proliferation rates were determined, apart from the autophagy assay and apoptosis determination by chip flow cytometry. Results: Metformin alone and especially metformin in association with PIAF increases oxidative stress within the cells by increasing the levels of lipid peroxids as well as decreasing the levels of reduced glutathione. The MTT cell proliferation assay showed decreased prolife­ration rates for the arm treated with metformin and with the combination of drugs in comparison with the control arm, proving high correlation with the oxidative stress results. The autophagy assay and determination of apoptosis by chip flow cytometry confirmed the results obtained in the previous assays. Conclusion: Metformin could be used in chemotherapy treatments to induce reactive oxygen species and increase the cytostatics effects within the tumor cell. Still, further experiments must be carried out on murine models before we can move on and use this drugs in the adjuvant setting for unresectable primary liver cancer.
issn 1812-9269
url https://nasplib.isofts.kiev.ua/handle/123456789/138685
citation_txt Metformin plus PIAF combination chemotherapy for hepatocellular carcinoma / B. Petrushev, C. Tomuleasa, O. Soritau, M. Aldea, T. Pop, S. Susman, G. Kacso, I. Berindan, A. Irimie, V. Cristea // Experimental Oncology. — 2012. — Т. 34, № 1. — С. 17-24. — Бібліогр.: 35 назв. — англ.
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first_indexed 2025-12-01T04:40:35Z
last_indexed 2025-12-01T04:40:35Z
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