Non-small-cell lung cancer (NSCLC) is one of the common malignant tumors, and multidrug resistance (MDR) and tumor metastasis limit the anticancer effect of NSCLC. Therefore, it is necessary to develop new anticancer drug that can inhibit MDR and metastasis of NSCLC. In the present study, we found that 5-(2-chlorophenyl)-4-(4-(3,5-dimethoxyphenyl)piperazine-1-carbonyl)-2H-1,2,3- triazole (MAY) displayed strong cytotoxic effect on A549 and taxol-resistant A549 cells (A549/Taxol cells). We further discovered that MAY led to G2/M phase arrest by inhibiting microtubule polymerization in both cells. Then MAY caused apoptosis by the mitochondrial pathway in A549 cells and through the extrinsic pathway in A549/Taxol cells. Interestingly, MAY was not a substrate for P-glycoprotein (P-gp), which was highly expressed in A549/Taxol cells, and MAY inhibited the expression and efflux function of P-gp. Furthermore, MAY inhibited epithelial-mesenchymal transition (EMT) by targeting Twist1 in A549/Taxol cells. In summary, our results suggest that MAY induces apoptosis in A549 and A549/Taxol cells and inhibits EMT in A549/Taxol cells. These findings suggest that MAY could provide a promising method for the treatment of NSCLC, especially for the treatment of resistant NSCLC.

中文翻译：

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MAY是一种新型微管蛋白抑制剂，可诱导A549和A549 / Taxol细胞凋亡，并抑制A549 / Taxol细胞上皮-间质转化。

非小细胞肺癌（NSCLC）是常见的恶性肿瘤之一，多药耐药（MDR）和肿瘤转移限制了NSCLC的抗癌作用。因此，有必要开发能够抑制MDR和NSCLC转移的新型抗癌药物。在本研究中，我们发现5-（2-氯苯基）-4-（4-（3,5-二甲氧基苯基）哌嗪-1-羰基）-2H-1,2,3-三唑（MAY）具有较强的细胞毒性对A549和抗紫杉醇的A549细胞（A549 / Taxol细胞）具有抗癌作用。我们进一步发现，MAY可能通过抑制两个细胞中的微管聚合而导致G2 / M期停滞。然后可能通过A549细胞的线粒体途径和A549 / Taxol细胞的外在途径引起凋亡。有趣的是，MAY不是P-糖蛋白（P-gp）的底物，P-糖蛋白在A549 / Taxol细胞中高度表达，可能抑制P-gp的表达和外排功能。此外，MAY通过靶向A549 / Taxol细胞中的Twist1抑制上皮-间质转化（EMT）。总之，我们的结果表明，MAY可以诱导A549和A549 / Taxol细胞凋亡，并抑制A549 / Taxol细胞中的EMT。这些发现表明，MAY可以为NSCLC的治疗，特别是耐药NSCLC的治疗提供有希望的方法。