A survivin double point mutant has potent inhibitory effect on the growth of hepatocellular cancer cells.
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.
Zhang
Rui
R
State Key Laboratory of Cancer Biology and Department of Biochemistry and Molecular Biology, Fourth Military Medical University, Xi'an, China.
Wang
Tao
T
Li
Kai Nan
KN
Qin
Wei Wei
WW
Chen
Rui
R
Wang
Kai
K
Jia
Lin Tao
LT
Zhao
Jing
J
Wen
Wei Hong
WH
Meng
Yan Ling
YL
Yao
Li Bo
LB
Yang
An Gang
AG
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
C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D000077022:Survivin