Astragaloside IV Enhances Cisplatin Chemosensitivity in Non-Small Cell Lung Cancer Cells Through Inhibition of B7-H3

Astragaloside IV Enhances Cisplatin Chemosensitivity in Non-Small Cell Lung Cancer Cells Through Inhibition of B7-H3
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DOI:
10.1159/000453175
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发表时间:
2016-01-01
影响因子:
--
通讯作者:
Jin, De-Hai
Jin, De-Hai
中科院分区:
医学1区
文献类型:
--
作者:
He, Cheng-Shi;Liu, Yi-Cheng;Jin, De-Hai

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背景:化疗耐药是非小细胞肺癌(NSCLC)化疗成功的主要障碍。黄芪甲苷(Astragaloside IV)是黄芪(Astragalus membranaceus)的主要成分,具有抗炎、抗癌和免疫调节作用。在本研究中,我们研究了黄芪甲苷在非小细胞肺癌细胞对顺铂化疗耐药性中的作用。研究方法:我们建立了黄芪甲苷IV抑制的NSCLC细胞系,包括A549,HCC 827和NCI-H1299,并评估了它们对顺铂的体外敏感性。此外,我们还检测了顺铂化疗后B7-H3的mRNA和蛋白水平。结果如下:我们发现,高浓度的黄芪甲苷(10,20,40 ng/ml)抑制NSCLC细胞的生长,而低浓度的黄芪甲苷(1,2.5,5 ng/ml)对细胞活力没有明显的细胞毒性。此外,与黄芪甲苷IV联合治疗显著增加了NSCLC细胞对顺铂的化疗敏感性。在分子水平上,在顺铂存在下,黄芪甲苷IV共处理显著抑制B7-H3的mRNA和蛋白水平。此外,B7-H3的异位表达减弱了黄芪甲苷IV在NSCLC细胞中对顺铂的细胞反应中的致敏作用。结论:这些结果表明,黄芪甲苷IV通过抑制B7-H3增强了对顺铂的化学敏感性,并且用黄芪甲苷IV治疗和抑制B7-H3可作为肺癌患者的潜在治疗方法。(C)2016作者(s)由S. Karger AG,巴塞尔
Background: Chemoresistance is a major obstacle to successful chemotherapy for human nonsmall cell lung cancer (NSCLC). Astragaloside IV, the component of Astragalus membranaceus, has been reported to exhibit anti-inflammation, anti-cancer and immunoregulatory properties. In the present study, we investigated the role of astragaloside IV in the chemoresistance to cisplatin in NSCLC cells. Methods: We established astragaloside IV-suppressed NSCLC cell lines including A549, HCC827, and NCI-H1299 and evaluated their sensitivity to cisplatin in vitro. In addition, we examined the mRNA and protein levels of B7-H3 in response to cisplatin-based chemotherapy. Results: We showed that high doses of astragaloside IV (10, 20, 40 ng/ml) inhibited NSCLC cell growth, whereas low concentrations of astragaloside IV (1, 2.5, 5 ng/ml) had no obvious cytotoxicity on cell viability. Moreover, combined treatment with astragaloside IV significantly increased chemosensitivity to cisplatin in NSCLC cells. On the molecular level, astragaloside IV co-treatment significantly inhibited the mRNA and protein levels of B7-H3 in the presence of cisplatin. In addition, ectopic expression of B7-H3 diminished the sensitization role of astragaloside IV in cellular responses to cisplatin in NSCLC cells. Conclusion: These results demonstrate that astragaloside IV enhances chemosensitivity to cisplatin via inhibition of B7-H3 and that treatment with astragaloside IV and inhibition of B7-H3 serve as potential therapeutic approach for lung cancer patients. (C) 2016 The Author(s) Published by S. Karger AG, Basel