title: Omega-3 Polyunsaturated Fatty Acids Enhance Cisplatin Efficacy in Gastric Cancer Cells by Inducing Apoptosis via ADORA1.
abstract: It has been suggested that administration of the omega-3 polyunsaturated fatty acids (ω-3 PUFAs), including docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), can alter the toxicity and/or activity of several anticancer drugs in in vitro and in vivo studies. Here, we investigated the ability of ω-3 PUFAs to potentiate the antineoplastic activity of cisplatin (CDDP) in gastric cancer cells. The increase in CDDP-induced growth inhibition was measured by the IC50 values obtained when the cells were incubated with CDDP alone or with CDDP plus DHA or EPA. DHA and EPA enhanced the growth-inhibition activity of increasing concentrations of CDDP. The interactions between CDDP and DHA or EPA at the cellular level were assessed through the combination index (CI) method of Chou-Talalay. The results demonstrated synergism between CDDP and DHA or EPA in MKN45 cells. Cell cycle analysis showed that the combination treatment increased G0/G1 phase and S phase arrest, and significantly increased the number of apoptotic cells. According to our previous study, ω -3 PUFAs induce apoptosis of gastric cells via ADORA1, a subtype of adenosine receptor functionally related to cell death. The ADORA1 mRNA and protein expression was higher in the combination treatment than in the individual treatments. Notable, when GC cells were pretreated with DPCPX, a selective ADORA1 antagonist, the combination treatment effect on apoptosis was significantly reduced. Our results suggest that ω-3 PUFAs enhance the antineoplastic effects of CDDP in gastric cancer cells, and the synergistic effect between ω-3 PUFAs and CDDP is partly dependent on activating the ADORA1-mediated apoptosis pathway.
authors.forename: Hong
authors.initials: H
authors.lastname: Sheng
authors.forename: Xuehua
authors.initials: X
authors.lastname: Chen
authors.forename: Binya
authors.initials: B
authors.lastname: Liu
authors.affiliation: Shanghai Key Laboratory of Gastric Neoplasms, Department of Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, China. leerockygood@yahoo.com.
authors.forename: Pu
authors.initials: P
authors.lastname: Li
authors.affiliation: Department of Clinical Nutrition, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 20025, China. Cwx103@163.com.
authors.forename: Weixin
authors.initials: W
authors.lastname: Cao
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D004357:Drug Synergism; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology*; D005753:Gastric Mucosa / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D012333:RNA, Messenger / Q000235:genetics; D043682:Receptor, Adenosine A1 / Q000235:genetics / Q000378:metabolism*; D013270:Stomach / Q000187:drug effects / Q000473:pathology; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D015525:Fatty Acids, Omega-3; D012333:RNA, Messenger; D043682:Receptor, Adenosine A1; D002945:Cisplatin