Thapsigargin Inhibits Proliferation,Migration And Invasion Of Ovarian Cancer Cells

Objective:Epithelial ovarian cancer has the highest mortality rate of all types of gynecological tumors,and is one of the most deadly gynecological malignancies in the world,having a serious impact on women’s lives.Due to the atypical clinical symptoms and the lack of effective screening methods,most patients are diagnosed in advanced stages,and postoperative recurrence and metastasis lead to poor prognosis of ovarian cancer.Therefore,it is important to find effective drugs for treating ovarian epithelial cancer.It has been reported that thapsigargin are effective inhibitors of a variety of tumors and induce cancer cell apoptosis by interfering with Ca²⁺homeostasis in the endoplasmic reticulum.This article investigates the effects of thapsigargin on the proliferation,migration,invasion and apoptosis of ovarian cancer cells and the possible mechanism.Methods:The effects of different concentrations of thapsigargin on the viability of ovarian cancer cell lines OVCAR3 and A2780 were measured using the thiazole blue（MTT）test.The 50%inhibitory concentration（IC50）was calculated and the optimal dose of thapsigargin was selected to treat ovarian cancer cells..Annexin V-FITC/PI double staining was used to detect cell apoptosis in experimental group and control group.Fluo-3-AM live cell staining was used to analyze changes in cytoplasmic calcium levels in ovarian cancer cells.Cell scratches and Transwell tests were performed to detect cells Changes in migration and invasion capabilities.Real-time quantitative PCR（QRT-PCR）technology and Western blotting were used to detect the expression of related indicators at the mRNA and protein levels.Results:We found that different concentrations of thapsigargin could reduce the cell viability of ovarian cancer cell lines OVCAR3（0.03125-1.0μmol/L）and A2780（0.0625-2.0μmol/L）in a dose-dependent manner.We selected the optimal concentration for the relevant tests.The results showed that thapsigargin can promote the apoptosis of ovarian cancer cells,increase the concentration of Ca²⁺in the cytoplasm,and reduce the migration and invasion ability of cells.In addition,after treatment with thapsigargin,the expression levels of Sarcoplasmic/endoplasmic reticulum Ca²⁺-ATP（SERCA2）,vascular endothelial growth factor A（VEGFA）,Apoptosis inhibitory gene Survivin,B-cell lymphoma-XL（Bcl-XL）,B-cell lymphoma-2（Bcl-2）were decreased,Transcription factor C/EBP-homologous protein（CHOP）expression levels increased.Conclusions:Thapsigargin may inhibit the proliferation,migration and invasion of ovarian cancer cells,and induce the ovarian cancer cells apoptosis by increasing the intracellular Ca²⁺concentration,which may guides a new direction for the treatment of ovarian cancer.