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

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.

Ropivacaine suppresses tumor biological characteristics of human hepatocellular carcinoma via inhibiting IGF-1R/PI3K/AKT/mTOR signaling axis

“…HepG2 cells were seeded in a 6-well plate at 1000 cells/well for 24 h. The following day, the cells were incubated with different concentrations (3.769, 7.538, and 15.076 mM) of ropivacaine for 2 weeks. Subsequently, the colonies were stained with 0.5% crystal violet for 20 min, and the colonies were photographed and counted [ 36 ].…”

“…Total protein was extracted using Radio Immunoprecipitation Assay (RIPA) buffer (P0013B, Beyotime, Jiangsu, China) containing 1 × protease inhibitor cocktail [ 36 ]. Total protein was separated by 12% SDS-PAGE and transferred onto polyvinylidene fluoride membranes (IPFL00010, Merck, MA, USA).…”

Higher Integrin Alpha 3 Beta1 Expression in Papillary Thyroid Cancer Is Associated with Worst Outcome

“…Moreover, α2β1 has been investigated as a potential therapeutic target in thyroid tumors. In TPC-1, a PTC cell line, ropivacaine suppresses proliferation, invasion, migration, and accelerate apoptosis via regulation of ITGA2 expression [40]. In our analysis in PTC, ITGA2 is positively associated with stage III, lymph node metastasis, minimal extrathyroidal extension, and intermediate-risk tumors.…”

Identification of Prognosis-Associated Biomarkers in Thyroid Carcinoma by a Bioinformatics Analysis

“…A previous study suggested that ropivacaine inhibited the proliferation, invasion and migration, as well as promoted apoptosis of thyroid cancer cells via regulating ITGA2 expression. 22 Targeting on ITGA3 could prevent thyroid cancer progression through disturbing cell cycling and autophagy. 23 A recent study indicated that galectin-3, encoded by LGALS3, has functioned as a serum marker for thyroid cancer diagnosis, and as a target for cancer imaging and therapy in the pre-clinical setting.…”