Impacts of Etomidate on the Proliferation, Migration and Immune Escape of Endometrial Cancer Cells by Regulating cGAS-STING Signal Pathway
CHEN Chuikai1*, WANG Qing1, WANG Xiaohua2
This paper aimed to investigate the effects of Eto (etomidate) on the proliferation, migration and immune escape of endometrial cancer cells by regulating the cGAS (cyclic guanosine-adenosine synthetase)- STING (interferon gene stimulating factor) signal pathway. Human endometrial cancer cell line HEC-1-A was treated with 10, 20, and 40 μg/mL Eto and labeled as low, medium, and high concentration Eto groups, and untreated HEC-1-A cells were used as control group. Meantime, on the basis of Eto high concentration, 1 μmol/L cGAS inhibitor RU.521 was added to treat HEC-1-A cells, which was recorded as Eto high concentration+RU.521 group. The proliferation and apoptosis of HEC-1-A cells in each group were detected by MTT method and flow cytometry. Transwell test was applied to detect the migration of HEC-1-A cells in each group. The expression levels of cGAS, STING and PD-L1 (immune escape protein) in HEC-1-A cells were detected by Western blot. The cells of each group were inoculated into the right back of mice to build a model of endometrial cell carcinoma transplanted tumor. After 4 weeks of feeding, the tumors were separated and weighed, and the number of CD8+ T cells in the tissues was determined by immunohistochemistry. The results show that compared with the control group, the apoptosis rate of HEC-1-A cells, the infiltration number of CD8+ T cells, the expression of cGAS and STING proteins in the Eto low, medium and high concentration groups increased, while the proliferation rate, migration number, expression of PD-L1 of HEC-1-A cells, and tumor mass were obviously decreased, in a concentration-dependent manner (P<0.05). Compared with Eto high concentration group, the apoptosis rate of HEC-1-A cells, the infiltration number of CD8+ T cells, the expression of cGAS and STING proteins in Eto high concentration+RU.521 group decreased, while the proliferation rate, migration number, expression of PD-L1 of HEC-1-A cells, and and tumor mass were obviously increased (P<0.05). In short, Eto can inhibit the proliferation, migration and immune escape of endometrial cancer cells and induce their apoptosis by regulating and activating the cGAS-STING signal pathway.
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