期刊
CANCER GENE THERAPY
卷 25, 期 11-12, 页码 300-308出版社
SPRINGERNATURE
DOI: 10.1038/s41417-018-0048-8
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Platinum-based chemotherapy is currently a standard treatment strategy for patients with gastric cancer. Eventhough it has been widely shown that microRNAs (miRNAs) are involved in tumor development, whether miRNAs have a role in chemosensitivity of gastric cancer cells to platinum-based treatment remain largely undefined. In this study, a cisplatinresistant gastric cancer cell line (SGC7901/DDP) with stable enhanced expression or knockdown of let-7b was generated. MTT and TUNEL assays were carried out to assess whether miR-let-7 is crucial for cell viability and apoptosis, respectively. In vitro luciferase reporter assay was performed to explore target genes of let-7b. Further, a subcutaneously transplanted tumor model in BALB/c nude mice was used to determine the impacts of let-7b on tumor growth in vivo. We observed that the let-7b-expression level of SGC7901/DDP cells was significantly lower than for its parental SGC7901 cells. Transfection of let-7b mimics was found to increase the cytotoxicity of DDP to SGC7901/DDP cells by inducing apoptosis. However, reversed cytotoxicity of DDP was observed in SGC7901/DDP cells with knockdown of let-7b. Luciferase reporter assay indicated that let-7b targeted AURKB in SGC7901/DDP cells. Knockdown of AURKB imitated the effect of let-7b overexpression on the sensitivity of SGC7901/DDP cells to DDP. Further investigation demonstrated that the SGC7901/ DDP primary tumor growth was significantly reduced by let-7b mimic transfection. These findings indicate that overexpression of let-7b might provide a potential strategic approach for attenuating DDP resistance in SGC7901/DDP human gastric cancer cells.
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