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  2. Overcoming cisplatin resistance by targeting the MTDH-PTEN interaction in ovarian cancer with sera derived from rats exposed to Guizhi Fuling wan extract

Overcoming cisplatin resistance by targeting the MTDH-PTEN interaction in ovarian cancer with sera derived from rats exposed to Guizhi Fuling wan extract

  • BMC Complement Med Ther. 2020 Feb 17;20(1):57. 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
Affiliations

Affiliations

  • 1 Zhang Zhongjing College of Chinese Medicine, Nanyang Institute of Technology, Nanyang, 473004, China
  • 2 Henan Key Laboratory of Zhang Zhongjing Formulae and Herbs for Immunoregulation, Nanyang Institute of Technology, Nanyang, 473004, China
  • 3 College of Pharmaceutical Science, Soochow University, Suzhou, 215123, China
  • 4 Department of Pharmacy, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China
Abstract

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.

Keywords

Chemotherapy resistance; Guizhi Fuling wan; MTDH; Ovarian Cancer; PTEN.

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