Ropivacaine inhibits proliferation, invasion, migration and promotes apoptosis of papillary thyroid cancer cells via regulating ITGA2 expression

罗哌卡因通过调控ITGA2表达抑制甲状腺乳头状癌细胞增殖、侵袭、迁移并促进其凋亡

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作者:Aichun Qin, Qiong Liu, Jingfang Wang

Abstract

The present study aimed to investigate the roles of Ropivacaine in papillary thyroid cancer (PTC) and identify the possible mechanisms. The expression of integrin alpha-2 (ITGA2) in TC cell lines was tested using Western blotting and RT-qPCR. Subsequently, the level of ITGA2 in human PTC cell line (TPC-1) was measured following intervention with a series of concentrations of Ropivacaine. Then, cell counting kit-8 (CCK-8) assay and colony formation assay were executed for detecting proliferation of cells after transfection with ITGA2 pcDNA3.1. The expression of proliferation-related protein was determined by Western blotting. Additionally, the abilities of TPC-1 cell invasion and migration were examined using Transwell assay and scratch wound healing assay. Apoptosis of TPC-1 cells was analyzed using TUNEL assay and the expressions of apoptosis-related proteins were tested via West blotting. The results suggested that ITGA2 was highly expressed in TC cell lines, especially in TPC-1 cells. Ropivacaine decreased the expression of ITGA2 in a dose-dependent manner. Moreover, after treatment with Ropivacaine, cell proliferation was inhibited accompanied by changes of proliferation-related protein expressions, which was reversed following co-transfection with ITGA2 pcDNA3.1. Furthermore, Ropivacaine concentration-dependently suppressed invasion and migration of TPC-1 cells, whereas these inhibitory effects were attenuated after ITGA2 overexpression. Furthermore, apoptosis was promoted, coupled with a decrease of Bcl-2 expression and increases of Bax, cleaved caspase-3 and cleaved caspase-9 expression, in Ropivacaine-treated TPC-1 cells, which was restored following ITGA2 overexpression. These findings demonstrated that Ropivacaine could suppress proliferation, invasion, migration, and accelerate apoptosis of PTC cells via regulating ITGA2 expression.

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