Lidocaine represses proliferation and cisplatin resistance in cutaneous squamous cell carcinoma via miR-30c/SIRT1 regulation

利多卡因通过 miR-30c/SIRT1 调节抑制皮肤鳞状细胞癌的增殖和顺铂耐药性

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作者:Tao Liu, Fei Jiang, Li-Yuan Yu, You-Yang Wu

Abstract

This study aimed to determine the effects of lidocaine on cell proliferation and cisplatin resistance in A431 human cutaneous squamous cell carcinoma (cSCC) cells and elucidate the underlying mechanism. Cell proliferation, colony numbers, and cisplatin resistance were determined in A431 or cisplatin-resistant A431 (A431-R) cells that were first transfected with miR-30c-inhibitor or miR-30c-mimic, respectively, and then treated with different concentrations of lidocaine, cisplatin, or both. The expression levels of miR-30c and Sirtuin 1 (SIRT1) in A431 and A431-R cells were determined by quantitative real-time polymerase chain reaction and Western blotting. Lidocaine suppressed A431 cell proliferation and cisplatin resistance in a dose- and time-dependent manner via the miR-30c/SIRT1 pathway. MiR-30c overexpression also suppressed cell proliferation and cisplatin resistance in A431 cells by directly targeting and downregulating SIRT1, thus enhancing the protective effects of lidocaine. Conversely, SIRT1 upregulation or miR-30c inhibition antagonized the inhibitory effects of lidocaine. Our results suggest that lidocaine may suppress the progression of cSCC by activating the miR-30c/SIRT1 pathway, indicating its promising potential as a treatment strategy for cSCC.

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