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首页> 外文期刊>Pharmaceutics >Achillin Increases Chemosensitivity to Paclitaxel, Overcoming Resistance and Enhancing Apoptosis in Human Hepatocellular Carcinoma Cell Line Resistant to Paclitaxel (Hep3B/PTX)
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Achillin Increases Chemosensitivity to Paclitaxel, Overcoming Resistance and Enhancing Apoptosis in Human Hepatocellular Carcinoma Cell Line Resistant to Paclitaxel (Hep3B/PTX)

机译：Achillin增加了对紫杉醇的化学敏感性，克服了对紫杉醇（Hep3B / PTX）耐药的人肝癌细胞系的耐药性并增强了其凋亡。

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Multidrug resistance (MDR) has become a major obstacle in the treatment of cancer, and is associated with mechanisms such as increased drug outflow, reduction of apoptosis, and/or altered drug metabolism. These problems can be mitigated by the coadministration of agents known as chemosensitizers, as they can reverse resistance to anticancer drugs and eventually resensitize cancer cells. We explore the chemosensitizing effect of Achillin, a guaianolide-type sesquiterpene lactone isolated from the Mexican medicinal plant Artemisia ludovisiana , to reverse MDR in Hep3B/PTX cells of hepatocellular carcinoma, which present resistance to paclitaxel (PTX). Achillin showed an important effect as chemosensitizer; indeed, the cytotoxic effect of PTX (25 nM) was enhanced, and the induction of G2/M phase cell cycle arrest and apoptosis were potentiated when combining with Achillin (100 μM). In addition, we observed that Achillin decreases P-gp levels and increases the intracellular retention of doxorubicin in Hep3B/PTX cells; in addition, homology structural modeling and molecular docking calculations predicted that Achillin interacts in two regions (M-site and R-site) of transporter drug efflux P-glycoprotein (P-gp). Our results suggest that the chemosensitizer effect demonstrated for Achillin could be associated with P-gp modulation. This work also provides useful information for the development of new therapeutic agents from guaianolide-type sesquiterpene lactones like Achillin.
机译：多药耐药性（MDR）已成为治疗癌症的主要障碍，并与诸如药物外流增加，细胞凋亡减少和/或药物代谢改变等机制相关。这些问题可以通过共同使用被称为化学增敏剂的药物来缓解，因为它们可以逆转对抗癌药的耐药性并最终使癌细胞重新敏化。我们探索Achillin的化学增敏作用，Achillin是从墨西哥药用植物Artemisia ludovisiana分离出的愈创木酚型倍半萜烯内酯，可逆转肝细胞癌Hep3B / PTX细胞中的MDR，后者对紫杉醇（PTX）具有抗药性。阿奇林显示出作为化学增敏剂的重要作用。实际上，与Achillin（100μM）结合使用时，增强了PTX（25 nM）的细胞毒性作用，并且增强了对G2 / M期细胞周期阻滞和凋亡的诱导。此外，我们观察到Achillin降低了Hep3B / PTX细胞中P-gp的水平并增加了阿霉素的细胞内滞留。此外，同源结构建模和分子对接计算预测Achillin在转运蛋白外排P-糖蛋白（P-gp）的两个区域（M位和R位）相互作用。我们的结果表明，对Achillin表现出的化学增敏作用可能与P-gp调节有关。这项工作还为开发从愈创木酚型倍半萜内酯（如阿奇林）的新型治疗剂提供了有用的信息。

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