Pentobarbital suppresses breast cancer proliferation by downregulating proliferating cell nuclear antigen.
Pentobarbital (PB), a barbiturate anesthetic, is widely used in many clinical treatments, including management of seizures and preoperative sedation. However, its potential role in cancer therapy remains underexplored. The inhibitory effects of PB on breast cancer proliferation were investigated in this study. Breast cancer cell lines MDA-MB-231 and MCF-7 were used to evaluate the effects of PB on cell proliferation. Proliferating cell nuclear antigen (PCNA) overexpression and knockdown models were established to assess its role in PB-mediated proliferation inhibition. Cell proliferation was measured using methyl thiazolyl tetrazolium (MTT), colony formation, and bromodeoxyuridine (BrdU) incorporation assays. Protein and mRNA expression levels of PCNA and cell cycle-related genes were analyzed by Western blot and real-time RT-PCR, respectively. Statistical analysis was performed using Student's t-test or one-way ANOVA. PB was found to inhibit cell proliferation and regulate the expression of cell cycle-related genes compared to the control group. Further analysis revealed that PB downregulated the expression of PCNA. Overexpression of PCNA increased the proliferation of MDA-MB-231 cells, while PCNA knockdown suppressed it. Notably, overexpression of PCNA could partially restore the proliferative capacity of MDA-MB-231 cells that had been inhibited by PB. The findings indicate that PB, in addition to its established roles as a sedative and anesthetic agent, suppresses breast cancer proliferation through the downregulation of PCNA expression. These results provides new theoretical evidence supporting the potential application of PB in cancer treatment.