AI Article Synopsis
- - 5-Fluorouracil (5-FU) is a key drug used to treat nasopharyngeal carcinoma (NPC), but cancer cells can become resistant to it over time.
- - The study found that reducing the expression of the oncogene BMI-1 in NPC cells makes them more susceptible to 5-FU by increasing apoptosis and lowering levels of protective proteins like BCL-2.
- - Inhibition of the PI3K/AKT pathway further enhances the effectiveness of 5-FU in cells with decreased BMI-1, suggesting that targeting BMI-1 could improve chemotherapy outcomes in NPC treatment.
Article Abstract
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.
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| http://dx.doi.org/10.1016/j.bbrc.2008.04.117 | DOI Listing |
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