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

Drug Dev Res. 2020 Sep;81(6):700-707. doi: 10.1002/ddr.21671. Epub 2020 Apr 20.

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.

Keywords: Ropivacaine; apoptosis; invasion; migration; proliferation; thyroid tumor.

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Cell Line
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Integrin alpha2 / genetics
  • Integrin alpha2 / metabolism
  • Ropivacaine / pharmacology*
  • Thyroid Cancer, Papillary / drug therapy*
  • Thyroid Cancer, Papillary / genetics
  • Thyroid Cancer, Papillary / metabolism
  • Thyroid Cancer, Papillary / pathology
  • Thyroid Neoplasms / drug therapy*
  • Thyroid Neoplasms / genetics
  • Thyroid Neoplasms / metabolism
  • Thyroid Neoplasms / pathology

Substances

  • Antineoplastic Agents
  • Integrin alpha2
  • Ropivacaine