Bmi-1 in gallbladder carcinoma: Clinicopathology and mechanism of regulation of human gallbladder carcinoma proliferation.

Abstract

Expression of Bmi-1 in gallbladder carcinoma and its clinicopathology and mechanisms of regulation of human gallbladder carcinoma cell proliferation were investigated. Fifty cases of gallbladder carcinoma specimens and 15 normal gallbladder tissues were subjected to immunohistochemical staining to detect the expression of Bmi-1 gene in gallbladder carcinoma and normal gallbladder tissues. Clinicopathological features were compared and analyzed. Bmi1-si RNA and Bmi1-NC vectors were transfected into GBC-SD gallbladder cancer cell lines. Expression of Bmi-1 in GBC-SD-Bmi1-si RNA, GBC-SD-Bmi1-NC and GBC-SD cells was detected by RT-qPCR. Cell proliferation was detected by CCK-8 assay. Flow cytometry was used to detect cell apoptosis. Protein expression was detected by western blot analysis. The positive expression rate of Bmi-1 protein in gallbladder carcinoma tissues was significantly higher than that in normal gallbladder tissues (P<0.05). Expression of Bmi-1 protein in gallbladder carcinoma was correlated with tumor differentiation and stage (P<0.05). Expression level of Bmi-1 in GBC-SD-Bmi1-si RNA was significantly lower than that in GBC-SD-Bmi1-NC and GBC-SD cells. The apoptosis rate of GBC-SD-Bmi1-si RNA cells was significantly higher than that of the two control groups. Compared with the control groups, the expression of anti-apoptotic protein Bcl-2 in GBC-SD-Bmi1-si RNA cells decreased, while the expression of proapoptotic protein Bax and caspase 3 increased, and the expression levels of cyclin D1 and CDK2 decreased. Positive expression rate of Bmi-1 protein in gallbladder carcinoma tissues was significantly higher than that in normal gallbladder tissue. Following inhibition of the expression of Bmi-1 in gallbladder cancer cell line GBC-SD, the growth cycle of cancer cells was prolonged and apoptotic rate increased. The results showed that a decreased expression of cyclin D1 and CDK2 may lead to delayed cell proliferation, decreased expression of anti-apoptotic protein Bcl-2, increased expression of pro-apoptotic protein Bax and caspase 3, leading to increased apoptosis.