MACC1 decreases the chemosensitivity of gastric cancer cells to oxaliplatin by regulating FASN expression

Abstract

The effect of chemotherapeutic agents is limited as a result of drug resistance, which demands prompt solutions provided by clinical studies. To date, the underlying mechanisms of chemotherapy resistance are relatively unknown. Metastasis-associated in colon cancer 1 (MACC1) is an oncogene associated with the progression and prognosis of gastric cancer (GC). Bioinformatic analysis revealed that MACCl is positively associated with fatty acid synthase (FASN), a major enzyme of lipogenesis, and drives chemoresistance to oxaliplatin in GC. Similar findings were demonstrated in two GC cell lines (BGC-823 and MKN-28) with MACCl ectopic expression. We next employed FASN inhibitor C75 or siFASN (small interfering RNA targeted to FASN) to block endogenous fatty acid metabolism and it was revealed that cell proliferation and chemoresistance to oxaliplatin induced by MACCl upregulation were attenuated by FASN blockade to various extents. Conclusively, these outcomes highlight a novel role of MACCl in GC cell lipogenesis, and suggest that MACCl may be an attractive target to decrease oxaliplatin resistance in GC.