Depletion of Bmi-1 enhances 5-fluorouracil-induced apoptosis and autophagy in hepatocellular carcinoma cells
- Authors:
- Jing Wu
- Dong Hu
- Rongbo Zhang
View Affiliations
Affiliations: Department of Medical Immunology, School of Medicine, Anhui University of Science and Technology, Huainan, Anhui 232001, P.R. China
- Published online on: July 16, 2012 https://doi.org/10.3892/ol.2012.805
-
Pages:
723-726
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Abstract
5-fluorouracil (5‑FU) is one of the standard chemoradiotherapy regimens for hepatocellular carcinoma (HCC) treatment. B‑cell‑specific Moloney murine leukemia virus insertion site 1 (Bmi‑1) has been demonstrated to regulate proliferation. Additionally, Bmi‑1 overexpression has been identified in HCC cell lines and correlates with the advanced invasive stage of tumor progression and poor prognosis. In this study, we examined the effects of 5‑FU treatment on cell growth in HCC cells with or without Bmi‑1 depletion. The IC50 values of 5‑FU were significantly decreased to a greater extent in cells with Bmi‑1 knockdown. Depletion of Bmi‑1 increased sensitivity of the cells to 5‑FU and increased apoptosis. Knockdown of endogenous Bmi‑1 led to a substantial reduction in the levels of phospho‑AKT and Bcl‑2 with a concomitant increase in the levels of Bax. Additionally, 5‑FU induced the conversion/turnover of microtubule-associated protein 1 light chain 3 (LC3). Knockdown of endogenous Bmi‑1 led to an increase in the levels of Beclin‑1 and the accumulation of LC3‑II. Together, these findings reveal that Bmi‑1 depletion enhanced the chemosensitivity of HCC cells by inducing apoptosis and autophagy, which is associated with the PI3K/AKT and Bcl‑2/Beclin‑1 pathways.
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