2. Academic Validation
  3. Survivin-targeted drug screening platform identifies a matrine derivative WM-127 as a potential therapeutics against hepatocellular carcinoma

Survivin-targeted drug screening platform identifies a matrine derivative WM-127 as a potential therapeutics against hepatocellular carcinoma

  • Cancer Lett. 2018 Jul 1;425:54-64. doi: 10.1016/j.canlet.2018.03.044.
Haisen Yin 1,  Risheng Que 2,  Chunying Liu 3,  Weidan Ji 3,  Bin Sun 3,  Xuejing Lin 3,  Qin Zhang 3,  Xinying Zhao 4,  Zhangxiao Peng 3,  Xiaofeng Zhang 3,  Haihua Qian 3,  Lei Chen 3,  Yonggang Yao 4,  Changqing Su 5
Affiliations

Affiliations

  • 1 Department of Molecular Oncology, Eastern Hepatobiliary Surgical Hospital & National Center of Liver Cancer, Second Military Medical University, Shanghai, 200438, China; Department of Gastroenterology, Jingzhou Central Hospital & Clinical Medical College, Yangtze University, Jingzhou, 434023, Hubei Province, China.
  • 2 Department of Surgery, Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310009, Zhejiang, China.
  • 3 Department of Molecular Oncology, Eastern Hepatobiliary Surgical Hospital & National Center of Liver Cancer, Second Military Medical University, Shanghai, 200438, China.
  • 4 Department of Gastroenterology, Jingzhou Central Hospital & Clinical Medical College, Yangtze University, Jingzhou, 434023, Hubei Province, China.
  • 5 Department of Molecular Oncology, Eastern Hepatobiliary Surgical Hospital & National Center of Liver Cancer, Second Military Medical University, Shanghai, 200438, China; Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical College, Xuzhou, 221002, Jiangsu, China. Electronic address: [email protected].
PMID: 29608986 DOI: 10.1016/j.canlet.2018.03.044
Abstract

Hepatocellular carcinoma (HCC) is the second leading cause of Cancer related death which needs novel drugs to improve patient outcome. Survivin overexpresses in HCC and contributes to HCC malignant progression. In this study, we established a Survivin-targeted drug screening platform, a cell model HepG2-Sur5P-EGFP-Sur3U stably transfected with lentivirus carrying an EGFP expression cassette, in which the EGFP expression was regulated by the upstream Survivin promoter and downstream Survivin 3'-UTR. By using this platform, we screened and easily identified one of matrine derivatives, WM-127, from hundreds of matrine derivatives. WM-127 was demonstrated to be a strong Survivin Inhibitor that inhibited cell proliferation, induced cell cycle arrest and Apoptosis of HCC cells, and suppressed the growth of HCC xenografted tumors in nude mice, suggesting that WM-127 might be a promising drug for HCC treatment. WM-127 exhibited less cytotoxicity in normal cells. Mechanistic studies showed that WM-127 suppressed the activity of Survivin/β-catenin pathway and the expression of Bax to induce cell cycle arrest and Apoptosis. Taken together, we constructed an economical, practical, efficient and convenient cell platform for screening the Survivin-targeted drugs from the enormous diversity of chemicals or factors, which would be a potential tool for antitumor drug research and development.

Keywords

Drug screening; Enhanced green fluorescent protein; Hepatocellular carcinoma; Matrine derivative; Survivin.

Figures
Products