Effects Of Endoplasmic Reticulum Stress On The Sensitivity Of Colon Cancer To The Anesthetic Drug Propofol

BackgroundPropofol,as a short-acting intravenous sedative,has been widely used in clinical practice,which plays a role in inhibiting tumor proliferation in the treatment of cancer cells.Studies have shown that propofol inhibits tumor proliferation mainly by inhibiting the STAT3 hotair WIF-1 /Wnt pathway.In recent years,the study of propofol has made great achievements,which provides a new therapeutic target for clinical antitumor therapy.Endoplasmic reticulum(ER)is one of the most important organelles in eukaryotic cells,mainly involved in protein synthesis,folding and secretion.ER stress is the stress response caused by the destruction of the homeostasis of the endoplasmic reticulum.To a certain extent,the endoplasmic reticulum can regulate itself to protect the function of the cell and restore its function;However,if the long-term stress state can induce cell apoptosis.Whether ER stress is involved in propofol’s effect on colon cancer cell death is unclear.ObjectivesTo clarify the biological behavior of propofol on colon cancer cells,explore the role of endoplasmic reticulum stress in the death of colon cancer cells induced by propofol,and provide a certain direction and basis for clinical treatment of colon cancer.Methods1.CCK8 method was used to detect the proliferation and survival of propofol on RKO、HCT-116 and SW480 colon cancer cells at different drug concentrations.2.Western blotting was used to detect the effects of propofol on the expression of endoplasmic reticulum stress proteins GRP78,P-EIF-2A and ATF4,and combined with endoplasmic reticulum stress inhibitors,the effect on cell survival,proliferation,and apoptosis-related proteins changes in the amount of expression.3.Flow cytometry was used to detect apoptosis of different concentrations of propofol in HCT-116 and RKO colon cancer cells.Results1.CCK8 results showed that different concentrations of propofol could significantly inhibit the survival rate and proliferation rate of RKO、HCT-116 and SW480 colon cancer cells.Drug concentration was negatively correlated with cell survival rate.The higher the drug concentration,the lower the cell survival rate,P<0.05.2.Flow cytometry results showed that with the increase of drug concentration,propofol also significantly increased apoptosis of colon cancer cells RKO and HCT-116.Moreover,apoptosis related protein cleaved caspase-3 was detected by Western blotting.Similarly,with the increase of drug concentration,the expression level also increased gradually.Gray value analysis,P<0.05.3.Western blotting results showed that the expressions of endoplasmic reticulum stress-related proteins GRP78,P-e IF-2A and ATF4 were significantly increased by different concentrations of propofol.Gray value analysis,P<0.05.4.CCK8 test results show that propofol combined with endoplasmic reticulum stress inhibitor can further reduce the survival rate of colon cancer cells caused by propofol,P<0.05.5.The results of flow cytometry showed that propofol combined with endoplasmic reticulum stress inhibitor 4-PBA and TUDCA further increased the apoptotic rate of colon cancer cells RKO and HCT-116.6.Western blotting results showed that compared with propofol alone,propofol combined with endoplasmic reticulum stress inhibitors 4-PBA and TUDCA had an effect on the apoptosis-related protein Cleaved-caspase-3,compared with propofol alone.The expression level of Pofol group increased,and the gray value analysis P<0.05.Conclusions1.Propofol causes the survival rate and survival rate of colon cancer cells to decrease,and induces apoptosis of colon cancer cells2.Propofol can induce endoplasmic reticulum stress in colon cancer cells.3.Propofol combined with endoplasmic reticulum stress inhibitor increases the cytotoxic effect of propofol on colon cancer cells.