Gastric cancer (GC) represents one of the most predominant malignancies with high incidence and mortality rates. Although traditional chemotherapeutics, including cisplatin are effective in the treatment of GC, patients often develop drug resistance in clinic. The present study aimed to explore the underlying mechanism of cisplatin-induced drug resistance in GC. The potential role of DNA demethylase ten-eleven translocation-2 (TET2) in modulating cisplatin resistance of GC cells was investigated. It was observed that TET2 was significantly decreased in cisplatin resistance SGC7901/DDP cells compared with non-resistant cells and TET2 overexpression markedly reduced the tolerance to cisplatin. Additionally, evidence was provided that TET2 regulated interleukin-6 levels in the tumor microenvironment through histone acetylation and therefore served an important role in the development of cisplatin resistance in GC cells. Taken together, the results suggested that TET2-mediated cisplatin resistance may represent a novel mechanism of drug resistance in GC cells and may offer novel treatment approaches.
Keywords: Cisplatin; Drug resistance; Gastric cancer; Ten-eleven translocation-2; interleukin-6.
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