Inhibiting the Proliferation of Colorectal Cancer Cells by Reducing TSPO/VDAC Expression

Iran J Public Health. 2023 Jul;52(7):1378-1389. doi: 10.18502/ijph.v52i7.13239.

Abstract

Background: We aimed to explore the mechanism of the effect of remimazolam (Rem) on the proliferation of colorectal cancer (CRC) cells with CRC as a disease context.

Methods: Translocation protein (TSPO) expression in CRC was determined by Western blotting and qRT-PCR in the Second Affiliated Hospital of Qiqihar Medical University from March 2019 to February 2022. TSPO-interacting proteins were predicted through string database. The proliferation was measured by CCK-8 and 5-ethynyl-2-deoxyuridine (EDU). The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT) and clonal colony on cells were formed to screen for the optimal concentration of Rem and to detect the viability. The expression of apoptosis-related proteins, Bcl-2 and P53, was determined by qRT-PCR and Western blotting. The effect of Rem on the expression of tumor markers, CEA and CA19-9, in CRC was examined through ELISA.

Results: TSPO expression in CRC tissues and cells was higher than that in ANT samples and normal intestinal epithelial cells. Over-expression of TSPO promoted the proliferation of HCT116 and the expression of tumor markers CEA and CA19-9 and inhibited the apoptosis of HCT116. Interference with TSPO inhibited the proliferation of HCT116 and the expression of CEA and CA19-9 and promoted the apoptosis of HCT116. 1 μg/mL Rem could inhibit the viability of HCT116, the proliferation of HCT116 and the expression of CEA and CA19-9, and improve the apoptosis of HCT116. TSPO could interact with VDAC and affect its protein expression, and Rem could inhibit the proliferation and the expression of CEA and CA19-9 through the TSPO/VDAC pathway, to promote its apoptosis.

Conclusion: Rem affects the proliferation of CRC cells by inhibiting the TSPO/VDAC pathway.

Keywords: Colorectal cancer; Remimazolam; Translocation protein.