Abstract：
In China, β-elemene, a sesquiterpene compound derived from Curcuma wenyujin, is clinically used to treat many human malignancies, including non-small cell lung cancer (NSCLC). Nonetheless, the role of β-elemene in regulating cisplatin sensitivity of NSCLC cells and the related mechanisms are not clear. This study was conducted to investigate the role of β-elemene in sensitizing NSCLC cells to cisplatin. In this work, cisplatin-resistant NSCLC cell lines were constructed. CCK-8, colony formation, and flow cytometry assays were executed to examine cell viability, growth, and apoptosis. MiR-17-5p and STAT3 expression levels in cells were detected by qRT-PCR. Western blot was executed to determine the expression levels of STAT3 and apoptosis-related proteins (Bax and Bcl-2) in the cells. Dual-luciferase reporter gene experiments were performed to verify the targeting relationship between miR-17-5p and STAT3. Herein, we report that, β-elemene inhibits the viability, and induces the apoptosis of cisplatin-resistant NSCLC cells. Additionally, β-elemene induces the upregulation miR-17-5p and downregulation of STAT3. STAT3 is validated to be a target of miR-17-5p in NSCLC cells. Additionally, the role of β-elemene to repress the viability of cisplatin-resistant NSCLC cells is partially counteracted by miR-17-5p inhibitor or STAT3 overexpression. In summary, our study suggests that β-elemene enhances cisplatin sensitivity of NSCLC cells by modulating miR-17-5p/STAT3 axis, and it may be a choice for the complementary treatment of NSCLC patients.
摘要：
在中国,β-榄香烯,一种来源于温郁金的倍半萜化合物，临床上用于治疗许多人类恶性肿瘤，包括非小细胞肺癌（NSCLC）。尽管如此，β-榄香烯在调节NSCLC细胞顺铂敏感性中的作用及相关机制尚不明确。本研究旨在探讨β-榄香烯在NSCLC细胞对顺铂敏感中的作用。在这项工作中,构建顺铂耐药的NSCLC细胞系。CCK-8,集落形成,和流式细胞术检测细胞活力，增长,和凋亡。通过qRT-PCR检测细胞中MiR-17-5p和STAT3的表达水平。进行Westernblot以确定细胞中STAT3和凋亡相关蛋白（Bax和Bcl-2）的表达水平。进行双荧光素酶报告基因实验以验证miR-17-5p与STAT3的靶向关系。在这里，我们报告说，β-榄香烯抑制活力，并诱导顺铂耐药NSCLC细胞凋亡。此外,β-榄香烯诱导miR-17-5p上调和STAT3下调。STAT3被证实是NSCLC细胞中miR-17-5p的靶标。此外,miR-17-5p抑制剂或STAT3过表达部分抵消了β-榄香烯抑制顺铂耐药NSCLC细胞活力的作用.总之,我们的研究提示β-榄香烯通过调节miR-17-5p/STAT3轴增强NSCLC细胞的顺铂敏感性,它可能是NSCLC患者补充治疗的一种选择。
