Mhaidat Nizar M, Thorne Rick F, de Bock Charles Edo, Zhang Xu Dong, Hersey Peter
Department of Clinical Pharmacy, Jordan University of Science and Technology, Irbid 22110, Jordan.
FEBS Lett. 2008 Jan 23;582(2):267-72. doi: 10.1016/j.febslet.2007.12.014. Epub 2007 Dec 18.
We have previously shown that Docetaxel-induced variable degrees of apoptosis in melanoma. In this report, we studied the beta-tubulin repertoire of melanoma cell lines and show that class III beta-tubulin expression correlated with Docetaxel-resistance. Sensitive cells showed low levels of class III beta-tubulin with little microtubular incorporation, whereas class III beta-tubulin expression was higher in resistant cells and was incorporated into the cytoskeleton. As proof of concept, abrogation of class III by siRNA reverted Docetaxel-resistant cells to a sensitive phenotype, restoring the microtubular polymerisation response and promoting high levels of apoptosis through Bax activation. These results suggest that phenotypic expression of beta-tubulin class III in melanoma may help identify patients with melanoma that can respond to taxanes.
我们之前已经表明，多西他赛可诱导黑色素瘤发生不同程度的凋亡。在本报告中，我们研究了黑色素瘤细胞系的β-微管蛋白库，并表明III类β-微管蛋白的表达与多西他赛耐药相关。敏感细胞显示III类β-微管蛋白水平较低，微管掺入较少，而耐药细胞中III类β-微管蛋白表达较高，并掺入细胞骨架。作为概念验证，通过小干扰RNA消除III类β-微管蛋白可使多西他赛耐药细胞恢复为敏感表型，恢复微管聚合反应，并通过激活Bax促进高水平的凋亡。这些结果表明，黑色素瘤中III类β-微管蛋白的表型表达可能有助于识别对紫杉烷类药物有反应的黑色素瘤患者。
