All-Trans Retinoic Acid Combination with Cisplatin and ۵-Fluorouracil Promote Cytotoxic Effect on AGS and KYSE-۳۰ Cell Lines

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 ۵-fluorouracil developed in gastric adenocarcinoma and squamous cell carcinoma. In this study, we investigated the combination treatment of ATRA with cisplatin and ۵-fluorouracil on gastric (AGS) and esophageal (KYSE-۳۰) cancer cell lines. Materials and Methods: KYSE-۳۰ and AGS cell lines were cultivated in RPMT-۱۶۴۰, including sub-toxic concentration of ATRA (۱۳.۶ and ۳.۶µM respectively) for ۶ days. Then, treat with cisplatin and ۵-fluorouracil for ۷۲h. The effects of combination treatment tested by MTT assay, ethidium bromide/acridin orange (EB/AO) staining and flow cytometry. Results: Determination of IC۵۰ (Inhibitory concentration of ۵۰%) with MTT assay showed, that combination treatment had cytotoxic effect in both cell lines. IC۵۰ value of the combined drugs was lower than the IC۵۰ of drugs alone. (P<۰/۰۵) The percentage of apoptotic cells was increased in comparison to drugs alone in EB/AO staining. (P<۰/۰۵) Furthermore there was an indication that the combination of ATRA with cisplatin caused increased cell cycle arrest at G۲/M in AGS and Kyse-۳۰ cells. Also, ATRA and ۵fu, induced increased the cell cycle arrest at G۱/S phase in Kyse-۳۰ and AGS cells (P<۰/۰۰۱). Conclusion: Our finding demonstrated that sub-toxic concentration of combination treatment of ATRA with cisplatin and ۵-fluorouracil had additive cytotoxic effects on KYSE-۳۰ and AGS cancer cell lines. References ۱- Takaishi S, Okumura T, Tu S, et al. Identification of gastric cancer stem cells using the cell surface marker CD۴۴. Stem Cells. ۲۰۰۹ ۲۷: ۱۰۰۶-۲۰. ۲- Enzinger P, Mayer R. Esophageal cancer. N Engl J Med. ۲۰۰۳ ۳۴۹: ۲۲۴۱-۵۲. ۳- Mohamadkhani A, Darvish Moghaddam S, Salmanroghani H, et al. 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Keywords: all-trans-Retinoic Acid , Cisplatin , ۵-Fluorouracil , KYSE-۳۰ cell lines , AGS cell lines