Li Caihong, Hong Li, Liu Cheng, Min Jie, Hu Ming, Guo Wenjun
Department of Gynaecology and Obstetrics, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan, 430060, Hubei, People's Republic of China.
Arch Gynecol Obstet. 2018 Feb;297(2):381-386. doi: 10.1007/s00404-017-4580-9. Epub 2017 Nov 4.
Multidrug resistance in malignant tumours hinders the treatment of tumours. Studies showed that astragalus polysaccharides (APS), one major active ingredient of astragalus, enhanced the sensitivity of non-small cell lung cancer and liver cancer cells to chemotherapeutic drug. However, the effect of APS on ovarian cancer is still unclear. In this study, we will examine the sensitizing effect of APS on SKOV3 cells to cisplatin and explore the possible mechanism.
MTT assay was employed to examine the viability of SKOV3 after treatment with APS and cisplatin. The cell apoptosis rate was determined by flow cytometry. The expression of Bax, Bcl-2, Caspase-3, and c-Jun N-terminal kinases 1/2 (JNK1/2) was measured using Western blotting and RT-PCR.
APS synergistically promoted the inhibitory effect of cisplatin on SKOV3 cell viability. Flow cytometry showed that APS promoted cisplatin-induced apoptosis of SKOV3 cell lines. Further studies showed that APS down-regulated the expression of Bcl2, increased the expression of Bax and caspase 3 and activated JNK1/2 signalling pathway. The JNK inhibitors significantly rescued the proliferation inhibition induced by the drugs.
Astragalus polysaccharides increased the sensitivity of SKOV3 cells to cisplatin potentially by activating the JNK pathway. The apoptosis-related genes may contribute to the process. Thus, APS may be useful for the treatment of ovarian cancer as an enhancer of chemosensitivity.
恶性肿瘤中的多药耐药性阻碍了肿瘤的治疗。研究表明,黄芪的一种主要活性成分黄芪多糖(APS)可增强非小细胞肺癌和肝癌细胞对化疗药物的敏感性。然而,APS对卵巢癌的作用仍不清楚。在本研究中,我们将检测APS对SKOV3细胞对顺铂的增敏作用,并探讨其可能的机制。
采用MTT法检测APS和顺铂处理后SKOV3细胞的活力。通过流式细胞术测定细胞凋亡率。采用蛋白质免疫印迹法和逆转录-聚合酶链反应(RT-PCR)检测Bax、Bcl-2、Caspase-3和c-Jun氨基末端激酶1/2(JNK1/2)的表达。
APS协同增强顺铂对SKOV3细胞活力的抑制作用。流式细胞术显示,APS促进顺铂诱导的SKOV3细胞系凋亡。进一步研究表明,APS下调Bcl2的表达,增加Bax和caspase 3的表达,并激活JNK1/2信号通路。JNK抑制剂显著挽救了药物诱导的增殖抑制。
黄芪多糖可能通过激活JNK途径增加SKOV3细胞对顺铂的敏感性。凋亡相关基因可能参与了这一过程。因此,APS作为化疗增敏剂可能对卵巢癌治疗有用。