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Exp Dermatol. 2013 Aug;22(8):518-23. doi: 10.1111/exd.12185. Epub 2013 Jun 27.

BCL2 and BCLxL are key determinants of resistance to antitubulin chemotherapeutics in melanoma cells.

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  • 1Department of Tumor Biology, Institute of Biomedical Sciences, Iwate Medical University, Yahaba-cho, Shiwa-gun, Japan.


Malignant melanoma is refractory to various chemotherapeutics including antitubulin agents such as paclitaxel. Previous studies have suggested a link between βIII-tubulin overexpression and paclitaxel resistance through alterations in the properties of the mitotic spindle. We found that paclitaxel treatment induced temporary mitotic arrest in 7 melanoma cell lines irrespective of the βIII-tubulin level, suggesting that βIII-tubulin had no significant influence on spindle properties. On the other hand, the amount of BCL2, an anti-apoptotic protein, was well correlated with paclitaxel resistance. Treatment of the paclitaxel-resistant cell lines with ABT-737, an inhibitor of BCL2 and BCLxL, or simultaneous knock-down of BCL2 and BCLxL dramatically increased the cells' sensitivity, while knock-down of MCL1, another member of the BCL2 family, had only a minimal effect. Our results suggest that the paclitaxel sensitivity of melanoma cells is attributable to apoptosis susceptibility rather than a change in spindle properties and that BCL2 and BCLxL play a pivotal role in the former.


BCL2; BCLxL; apoptosis; melanoma; paclitaxel

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