Downregulation of MTMR3 by atorvastatin calcium suppresses autophagy and inhibits proliferation and migration of colorectal cancer HCT116 cells
LIU Long-fei,LIU Yan-li,CHEN Yan-hua
Department of Gastrointestinal Surgery，Nanhua Hospital Affiliated to University of South China，Hengyang(421000)，China
Abstract:
Objective To investigate the mechanisms underlying the induction of autophagy inhibition and the subsequent suppression of proliferation and migration in colorectal cancer (CRC) HCT116 cells by atorvastatin calcium (ATO). Methods Firstly, immunohistochemical staining was performed to detect the expression of MTMR3 and P62 in CRC tissues and adjacent non-cancerous tissues. Secondly, HCT116 cells were treated with ATO at concentrations of 0, 12.5, 25, 50, and 100 μmol/L for 24 hours, and cell viability was assessed using the MTT assay. Thirdly, HCT116 cells were treated with ATO at concentrations of 12.5, 25, and 37.5 μmol/L, and colony formation and cell migration assays were conducted. Western blot analysis was performed to examine the expression of MTMR3, as well as autophagy-related proteins LC3 and P62. Lastly, HCT116 cells were treated with ATO in combination with si-MTMR3 or autophagy inhibitor chloroquine, or with chloroquine alone. Cell viability, colony formation, and migration capacity of HCT116 cells were assessed, and the expression of MTMR3, LC3, and P62 proteins was examined using Western blot analysis. Results The results showed that MTMR3 and P62 were highly expressed in CRC tissues. Treatment of HCT116 cells with ATO resulted in decreased cell viability, colony formation, and migration capacity, which correlated with reduced expression of MTMR3 and P62, as well as an increase in the LC3II/I ratio, indicative of autophagy induction. Moreover, the inhibitory effects of ATO on HCT116 cells were reversed by the autophagy inhibitor chloroquine. Additionally, si-MTMR3 exhibited a synergistic inhibitory effect with ATO on HCT116 cells and induced autophagy. Conclusion ATO suppresses proliferation and migration of HCT116 cells in CRC, potentially through the downregulation of MTMR3 expression and induction of cellular autophagy.
