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雷公藤甲素通过抑制AKT的磷酸化使顺铂耐药的人上皮性卵巢癌致敏。

Triptolide sensitizes cisplatin-resistant human epithelial ovarian cancer by inhibiting the phosphorylation of AKT.

作者信息

Huang Genhua, Hu Hui, Zhang Yao, Zhu Yinfang, Liu Junli, Tan Buzhen, Chen Tingtao

机构信息

Department of Obstetrics & Gynecology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, PR China.

Institute of Translational Medicine, Nanchang University, Nanchang, Jiangxi 330031, PR China.

出版信息

J Cancer. 2019 Jun 2;10(13):3012-3020. doi: 10.7150/jca.30669. eCollection 2019.

Abstract

Advanced and chemotherapy-resistant ovarian cancer causes high mortality of ovarian cancer, and it is important to find safe and effective drugs to reduce the chemotherapeutic resistance of ovarian cancer. In our study, we attempted to clarify the resistance mechanisms of SKOV3/DDP cells and evaluated the sensitization to triptolide (TPL) . Our results indicated that the overexpression of AKT and p-AKT greatly enhanced the cisplatin (DDP) tolerance of SKOV3/DDP, and the combination of DDP+TPL had a significant tumour inhibition effect compared to DDP treatment (p<0.05), via reducing the expressions of p-PI3K, p-Akt, Survivin, VEGF and MMP-2, and the increase of Caspase-3. Collectively, these results suggest that the synergistic anticancer effect of TPL and DDP warrants their potential clinical applications in further.

摘要

晚期及化疗耐药的卵巢癌导致卵巢癌的高死亡率,因此寻找安全有效的药物以降低卵巢癌的化疗耐药性很重要。在我们的研究中,我们试图阐明SKOV3/DDP细胞的耐药机制,并评估其对雷公藤内酯醇(TPL)的敏感性。我们的结果表明,AKT和p-AKT的过表达极大地增强了SKOV3/DDP对顺铂(DDP)的耐受性,并且与DDP治疗相比,DDP+TPL组合具有显著的肿瘤抑制作用(p<0.05),这是通过降低p-PI3K、p-Akt、Survivin、VEGF和MMP-2的表达以及增加Caspase-3来实现的。总体而言,这些结果表明TPL和DDP的协同抗癌作用值得在进一步的研究中进行潜在的临床应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d35/6590046/3bce46c1270f/jcav10p3012g001.jpg

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