Overcoming cisplatin resistance by targeting the MTDH-PTEN interaction in ovarian cancer with sera derived from rats exposed to Guizhi Fuling wan extract
| Autor: | Xueyun Cao, Yubing Zhou, Lei Yang, Xiaojuan Guo, Li Han, Zhong Chen, Hua Bian |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
PTEN MTDH Antineoplastic Agents Biology Immunofluorescence 03 medical and health sciences 0302 clinical medicine Cell Line Tumor medicine Animals Humans Tensin Rats Wistar Ovarian Neoplasms Cisplatin medicine.diagnostic_test PTEN Phosphohydrolase Membrane Proteins RNA-Binding Proteins Colocalization lcsh:Other systems of medicine lcsh:RZ201-999 medicine.disease Guizhi Fuling wan Ovarian Cancer Rats Blot 030104 developmental biology Complementary and alternative medicine Drug Resistance Neoplasm 030220 oncology & carcinogenesis Cancer research biology.protein Female Chemotherapy resistance Ovarian cancer Research Article Drugs Chinese Herbal medicine.drug |
| Zdroj: | BMC Complementary Medicine and Therapies BMC Complementary Medicine and Therapies, Vol 20, Iss 1, Pp 1-14 (2020) |
| ISSN: | 2662-7671 |
| DOI: | 10.1186/s12906-020-2825-9 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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