Details

Autor(en) / Beteiligte

• Qin, Li
• Zhang, Xing
• Zhang, Ling
• Feng, Yan
• Weng, Gui-Xiang
• Li, Man-Zhi
• Kong, Qing-Li
• Qian, Chao-Nan
• Zeng, Yi-Xin
• Zeng, Mu-Sheng
• Liao, Duan-Fang
• Song, Li-Bing

Titel

Downregulation of BMI-1 enhances 5-fluorouracil-induced apoptosis in nasopharyngeal carcinoma cells

Ist Teil von

• Biochemical and biophysical research communications, 2008-07, Vol.371 (3), p.531-535

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2008

Quelle

MEDLINE

Beschreibungen/Notizen

• 5-Fluorouracil (5-FU) is an important chemotherapeutic agent for nasopharyngeal carcinoma (NPC). However, drug resistance may occur after several cycles of 5-FU-based chemotherapy. The oncogene B-cell-specific Moloney murine leukemia virus insertion site 1 (BMI-1) has been shown to be involved in the protection of cancer cells from apoptosis. In this study, 5-FU treatment could increase the percentage of apoptotic NPC cells among BMI-1/RNAi-transfected cells than that among cells transfected with the empty vector. The 50% inhibitory concentration (IC 50) values of 5-FU were significantly decreased to a greater extent in the cells transfected with BMI-1/RNAi. Most importantly, the expression of phospho-AKT and the anti-apoptotic protein BCL-2 were downregulated in the cells in which BMI-1 expression was inhibited, whereas the apoptosis-inducer BAX was observed to be upregulated. Abrogation of AKT pathway by a PI3K inhibitor could not further increase the sensitivity to 5-FU in the cells with reduced BMI-1 expression. Taken together, BMI-1 depletion enhanced the chemosensitivity of NPC cells by inducing apoptosis; which is associated with inhibition of the PI3K/AKT pathway.