当前位置: X-MOL 学术BMC Complement. Altern. Med. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Overcoming cisplatin resistance by targeting the MTDH-PTEN interaction in ovarian cancer with sera derived from rats exposed to Guizhi Fuling wan extract.
BMC Complementary and Alternative Medicine ( IF 4.782 ) Pub Date : 2020-02-17 , DOI: 10.1186/s12906-020-2825-9
Li Han 1, 2 , Xueyun Cao 1, 2 , Zhong Chen 3 , Xiaojuan Guo 1, 2 , Lei Yang 1, 2 , Yubing Zhou 4 , Hua Bian 1, 2
Affiliation  

BACKGROUND The well-known traditional Chinese herbal formula Guizhi Fuling Wan (GFW) was recently reported to improve the curative effects of chemotherapy for ovarian cancer with few clinical side effects. The present study aimed to investigate the reversal mechanism of sera derived from rats exposed to Guizhi Fuling Wan extract (GFWE) in cisplatin-resistant human ovarian cancer SKOV3/DDP cells; the proteins examined included phosphatase and tensin homolog (PTEN) and metadherin (MTDH), and the possible protein interaction between PTEN and MTDH was explored. METHODS GFWE was administered to healthy Wistar rats, and the sera were collected after five days. The PubMed and CNKI databases were searched for literature on the bioactive blood components in the sera. The systemsDock website was used to predict potential PTEN/MTDH interactions with the compounds. RT-qPCR, western blotting, and immunofluorescence analyses were used to analyze the mRNA and protein levels of MTDH and PTEN. Laser confocal microscopy and coimmunoprecipitation (co-IP) were used to analyze the colocalization and interaction between MTDH and PTEN. RESULTS Sixteen bioactive compounds were identified in GFWE sera after searching the PubMed and CNKI databases. The systemsDock website predicted the potential PTEN/MTDH interactions with the compounds. RT-qPCR, western blotting, and immunofluorescence analyses showed decreased MTDH expression and increased PTEN expression in the sera. Laser confocal microscopy images and coimmunoprecipitation (co-IP) analyses demonstrated that a colocalization and interaction occurred between MTDH and PTEN, and the addition of the sera changed the interaction status. CONCLUSIONS GFWE restored sensitivity to cisplatin by inhibiting MTDH expression, inducing PTEN expression, and improving the interaction between MTDH and PTEN in SKOV3/DDP cells, and these proteins and their interaction may serve as potential targets for cancer treatment. The sera may represent a new source of anticancer compounds that could help to manage chemoresistance more efficiently and safely.

中文翻译:

通过靶向MTDH-PTEN相互作用克服卵巢癌中顺铂耐药性,该血清来自暴露于桂枝Fu灵丸提取物的大鼠血清。

背景技术最近有报道称,著名的中草药配方桂枝Fu灵丸(GFW)可以提高卵巢癌化疗的疗效,并且几乎没有临床副作用。本研究旨在研究暴露于桂枝Fu灵丸提取物(GFWE)的大鼠血清在顺铂耐药人卵巢癌SKOV3 / DDP细胞中的逆转机制。检测的蛋白质包括磷酸酶和张力蛋白同源物(PTEN)和间粘素(MTDH),并探讨了PTEN和MTDH之间可能的蛋白质相互作用。方法对健康Wistar大鼠给予GFWE,5天后收集血清。在PubMed和CNKI数据库中搜索有关血清中生物活性血液成分的文献。systemsDock网站用于预测与化合物的潜在PTEN / MTDH相互作用。使用RT-qPCR,蛋白质印迹和免疫荧光分析来分析MTDH和PTEN的mRNA和蛋白水平。激光共聚焦显微镜和免疫共沉淀(co-IP)被用来分析MTDH和PTEN之间的共定位和相互作用。结果通过搜索PubMed和CNKI数据库,在GFWE血清中鉴定出16种生物活性化合物。systemsDock网站预测了PTEN / MTDH与化合物的潜在相互作用。RT-qPCR,western blotting和免疫荧光分析显示,血清中MTDH表达降低,PTEN表达升高。激光共聚焦显微镜图像和免疫共沉淀(co-IP)分析表明,MTDH和PTEN之间发生了共定位和相互作用,血清的添加改变了相互作用状态。结论GFWE通过抑制MTDH的表达,诱导PTEN的表达以及改善SKDH3 / DDP细胞中MTDH与PTEN的相互作用而恢复了对顺铂的敏感性,这些蛋白及其相互作用可能成为癌症治疗的潜在靶点。血清可能代表了一种新的抗癌化合物来源,可以帮助更有效,更安全地控制化学耐药性。
更新日期:2020-04-01
down
wechat
bug