title: A survivin double point mutant has potent inhibitory effect on the growth of hepatocellular cancer cells.
abstract: Survivin is an attractive target in cancer therapy. Previous studies have demonstrated that survivin dominant-negative mutants T34A and C84A were able to induce apoptosis in cancer cells. Given that they had different mechanisms in inducing apoptosis, our study was undertaken to determine whether a survivin double point mutant (TC34,84AA) could achieve more potent inhibitory effect on the growth of hepatocellular cancer cells. Adenoviruses expressing survivin mutants were constructed and transduced into hepatocellular cancer cells. The inhibitory effect of the survivin mutants on cancer cell growth was measured. Transduction of cancer cells with all three survivin mutants resulted in significant apoptosis. Compared with survivin mutants T34A or C84A alone, the cancer killing effect of survivin TC34,84AA was much stronger. In addition, the survivin mutants were more sensitive than wild type survivin to the degradation in the ubiquitin-proteasome pathway. Our results suggest that adenovirus-delivered dominant-negative survivin TC34,84AA promotes apoptosis-mediated hepatocellular carcinoma suppression, and could potentially be a promising candidate for cancer therapies.
authors.affiliation: State Key Laboratory of Cancer Biology and Department of Biochemistry and Molecular Biology, Fourth Military Medical University, Xi'an, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Zhang
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.forename: Kai Nan
authors.initials: KN
authors.lastname: Li
authors.forename: Wei Wei
authors.initials: WW
authors.lastname: Qin
authors.forename: Rui
authors.initials: R
authors.lastname: Chen
authors.forename: Kai
authors.initials: K
authors.lastname: Wang
authors.forename: Lin Tao
authors.initials: LT
authors.lastname: Jia
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.forename: Wei Hong
authors.initials: WH
authors.lastname: Wen
authors.forename: Yan Ling
authors.initials: YL
authors.lastname: Meng
authors.forename: Li Bo
authors.initials: LB
authors.lastname: Yao
authors.forename: An Gang
authors.initials: AG
authors.lastname: Yang
mesh_terms: D000256:Adenoviridae; D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000628:therapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008113:Liver Neoplasms / Q000628:therapy*; D008869:Microtubule-Associated Proteins / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics*; D017354:Point Mutation; D000077022:Survivin
chemical_list: C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D000077022:Survivin