Liu Yang, Wang Shuyue, Yang Weining
Department of Anesthesiology, The Second Affiliated Hospital of Qiqihar Medical University, Qiqihar 161000, China.
Operating Room, The Second Affiliated Hospital of Qiqihar Medical University, Qiqihar 161000, China.
Iran J Public Health. 2023 Jul;52(7):1378-1389. doi: 10.18502/ijph.v52i7.13239.
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.
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.
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.
Rem affects the proliferation of CRC cells by inhibiting the TSPO/VDAC pathway.
以结直肠癌（CRC）为疾病背景，我们旨在探究瑞马唑仑（Rem）对CRC细胞增殖的影响机制。
于2019年3月至2022年2月在齐齐哈尔医学院附属第二医院，通过蛋白质免疫印迹法和qRT-PCR检测CRC中易位蛋白（TSPO）的表达。通过字符串数据库预测与TSPO相互作用的蛋白。采用CCK-8和5-乙炔基-2'-脱氧尿苷（EDU）检测细胞增殖情况。通过3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐（MTT）法和细胞克隆集落形成实验筛选Rem的最佳浓度并检测细胞活力。通过qRT-PCR和蛋白质免疫印迹法检测凋亡相关蛋白Bcl-2和P53的表达。通过酶联免疫吸附测定（ELISA）检测Rem对CRC中肿瘤标志物癌胚抗原（CEA）和糖类抗原19-9（CA19-9）表达的影响。
CRC组织和细胞中TSPO的表达高于正常对照样本和正常肠上皮细胞。TSPO的过表达促进了人结肠癌细胞系HCT116的增殖以及肿瘤标志物CEA和CA19-9的表达，并抑制了HCT116的凋亡。干扰TSPO可抑制HCT116的增殖以及CEA和CA19-9的表达，并促进HCT116的凋亡。1μg/mL的Rem可抑制HCT116的活力、HCT116的增殖以及CEA和CA19-9的表达，并促进HCT116的凋亡。TSPO可与电压依赖性阴离子通道（VDAC）相互作用并影响其蛋白表达，Rem可通过TSPO/VDAC途径抑制HCT116的增殖以及CEA和CA19-9的表达，从而促进其凋亡。
Rem通过抑制TSPO/VDAC途径影响CRC细胞的增殖。
