افزایش اثرات درمانی سیس پلاتین و 5- فلورواوراسیل بر روی رده‌های سلولی AGS و KYSE-30 با استفاده از تیمار ترکیبی رتینوئیک اسید تمام ترانس

Backgrounds and Objectives: All-trans retinoic acid (ATRA) which is a derivative of vitamin A, exert fundamental effects on regulation of cell growth, differenation and apoptosis. Recently, resistance to cisplatin and 5-fluorouracil developed in gastric adenocarcinoma and squamous cell carcinoma. In this study, we investigated the combination treatment of ATRA with cisplatin and 5-fluorouracil on gastric (AGS) and esophageal (KYSE-30) cancer cell lines. Materials and Methods: KYSE-30 and AGS cell lines were cultivated in RPMT-1640, including sub-toxic concentration of ATRA (13.6 and 3.6µM respectively) for 6 days. Then, treat with cisplatin and 5-fluorouracil for 72h. The effects of combination treatment tested by MTT assay, ethidium bromide/acridin orange (EB/AO) staining and flow cytometry. Results: Determination of IC50 (Inhibitory concentration of 50%) with MTT assay showed, that combination treatment had cytotoxic effect in both cell lines. IC50 value of the combined drugs was lower than the IC50 of drugs alone. (P<0/05) The percentage of apoptotic cells was increased in comparison to drugs alone in EB/AO staining. (P<0/05) Furthermore there was an indication that the combination of ATRA with cisplatin caused increased cell cycle arrest at G2/M in AGS and Kyse-30 cells. Also, ATRA and 5fu, induced increased the cell cycle arrest at G1/S phase in Kyse-30 and AGS cells (P<0/001). Conclusion: Our finding demonstrated that sub-toxic concentration of combination treatment of ATRA with cisplatin and 5-fluorouracil had additive cytotoxic effects on KYSE-30 and AGS cancer cell lines. References 1- Takaishi S, Okumura T, Tu S, et al. Identification of gastric cancer stem cells using the cell surface marker CD44. Stem Cells. 2009 27: 1006-20. 2- Enzinger P, Mayer R. Esophageal cancer. N Engl J Med. 2003 349: 2241-52. 3- Mohamadkhani A, Darvish Moghaddam S, Salmanroghani H, et al. 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