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目的研究南强菌素(DM)对肿瘤细胞紫杉醇耐药性的逆转作用并探讨其逆转机制。方法 MTT法检测南强菌素对A549/T耐药细胞与A549敏感细胞的毒性及其对紫杉醇敏感性的影响,以Annexin V法检测细胞凋亡率和Rh123在耐药细胞中的积累,HPLC测定细胞内紫杉醇的蓄积量,Western blotting检测Ⅲ型β微管蛋白的表达水平。结果南强菌素可显著提高A549/T细胞对紫杉醇的敏感性,增加紫杉醇诱导耐药细胞凋亡率,增强A549/T细胞中紫杉醇和Rh123的蓄积能力,同时,亦可明显抑制A549/T细胞中Ⅲ型β微管蛋白的表达水平。结论南强菌素可有效提高耐药细胞对紫杉醇的敏感性,逆转A549/T细胞对紫杉醇的耐药作用,其逆转机制可能与南强菌素抑制耐药肿瘤细胞膜上耐药蛋白P-糖蛋白的外泵转运功能和干扰Ⅲ型β微管蛋白的表达水平有关。
Objective To investigate the reversal effect of streptozotocin (ST) on paclitaxel resistance and to explore its mechanism of reversal. Methods MTT assay was used to determine the cytotoxicity of SST on A549 / T cells and A549-sensitive cells and its sensitivity to paclitaxel. The apoptosis rate and the accumulation of Rh123 in drug-resistant cells were detected by Annexin V assay. HPLC The amount of intracellular paclitaxel was measured, and the expression of type III tubulin was detected by Western blotting. Results Nanothricin can significantly increase the sensitivity of A549 / T cells to paclitaxel, increase the apoptosis rate of paclitaxel-induced drug-resistant cells and enhance the accumulation capacity of paclitaxel and Rh123 in A549 / T cells, meanwhile, also inhibit A549 / T Expression of type III tubulin in cells. Conclusions Strychnine can effectively increase the sensitivity of paclitaxel to drug-resistant cells and reverse the drug-resistant effect of paclitaxel in A549 / T cells. The reversal mechanism may be related to the inhibitory effect of cefotaxime on drug-resistant protein P-glycoprotein The extra-pump transport of proteins is related to the level of expression of type III beta tubulin.