Modifying effects of 5-azacytidine on metal-containing proteins profile in guerin carcinoma with different sensitivity to cytostatics

• Опубліковано в: : Experimental Oncology
• Дата: 2016
• Автори: Chekhun, V.F., Lozovska, Y.V., Naleskina, L.A., Borikun, T.V., Burlaka, A.P., Todor, I.N., Demash, D.V., Yalovenko, T.M., Zadvornyi, T.V., Pavlova, A.O., Storchay, D.M., Lukianova, N.Yu.
• Формат: Стаття
• Мова: English
• Опубліковано: Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України 2016
• Теми: Original contributions
• Онлайн доступ: https://nasplib.isofts.kiev.ua/handle/123456789/137697
• Назва журналу: Digital Library of Periodicals of National Academy of Sciences of Ukraine
• Цитувати: Modifying effects of 5-azacytidine on metal-containing proteins profile in guerin carcinoma with different sensitivity to cytostatics / V.F. Chekhun, Y.V. Lozovska, L.A. Naleskina, T.V. Borikun, A.P. Burlaka, I.N. Todor, D.V. Demash, T.M. Yalovenko, T.V. Zadvornyi, A.O. Pavlova, D.M. Storchay, N.Yu. Lukianova // Experimental Oncology. — 2016 — Т. 38, № 4. — С. 283-287. — Бібліогр.: 16 назв. — англ.

Aim: To assess the influence of the treatment with 5-azacytidine (5-aza) on the profile of metal-containing proteins and factors of their regulation in Guerin carcinoma cells in vivo. Materials and Methods: The study was conducted on Wistar rats transplanted with wild-type Guerin carcinoma (Guerin/WT) and its strains resistant to cisplatin (Guerin/CP) or doxorubicin (Guerin/Dox). Animals were distributed in 6 groups treated with 5-aza and control animals without treatment. 5-Aza was injected by i.v. route (1 injection in 4 days at a dose of 2 mg/kg starting from the 4th day after tumor transplantation, 4 injections in total). Ferritin levels in blood serum and tumor tissue were measured by ELISA, transferrin and free iron complexes — by low-temperature EPR, miRNA-200b, -133a and -320a levels and promoter methylation — by real-time quantitative reverse transcription polymerase chain reaction. Results: The study has shown that 5-aza treatment caused demethylation of promoter regions of fth1 and tfr1 genes in all studied Guerin carcinoma strains. 5-Aza treatment resulted in a significant decrease of ferritin levels in tumor tissue (by 32.1% in Guerin/WT strain, by 29.8% in Guerin/Dox and by 69.1% in Guerin/CP). These events were accompanied by 3.5-fold and 2-fold increase of free iron complexes levels in tumor tissue of doxorubicin and cisplatin resistant strains, respectively. Also, 5-aza treatment resulted in significantly elevated levels of miR-200b, -133a, 320a expression in tumor tissue. After 5-aza treatment, ferritin levels in blood serum of animals with Guerin/Dox were increased by 23.9%, while in Guerin/Wt and Guerin/CP they were decreased by 17 and 16%, respectively. Conclusion: Alterations of epigenetic regulation upon in vivo treatment with 5-aza change the levels of metal-containing proteins due to DNA demethylation and altered miRNA expression profiles in Guerin carcinoma cells.