Knockdown of survivin expression by siRNA induces apoptosis of hepatocellular carcinoma cells

Abstract

Survivin, a newly identified member of IAP family, is a powerful apoptosis-inhibiting factor. It is expressed in embryonic tissues as well as in the majority of human cancers, but not in most normal adult tissues. The cancer-specific expression of survivin makes it a potential target for cancer treatment. A survivin-specific small inhibitory RNA (siRNA) was introduced into hepatocellular carcinoma cells to investigate its effect on cancer cell apoptosis, growth and sensitivity to chemotherapeutic drugs. It was found that expressions of survivin protein and proliferation index (PI) in siRNA groups were significantly decreased, the apoptosis index (AI) of siRNA groups was significantly higher than those of others groups, and the growth inhibition rate (GIR) of chemotherapeutic drugs in siRNA groups were significantly higher than those of other groups. Our study suggests that the expression of survivin may be significantly decreased in hepG2 cell after siRNA transfection. siRNA targeting survivin could induce cell apoptosis, inhibit cell proliferation and sensitize hepatocarcinoma cells to chemotherapy. Our findings provide preliminary evidence for the therapeutic use of survivin-targeted RNA interference for human tumors that express high levels of this molecule.

Keywords

survivin / siRNA / apoptosis hepatocellular carcinoma

References

[1] JohnsonM. E., HowerthE. W.. Survivin: A Bifunctional Inhibitor of Apoptosis Protein. Vet Pathol, 2004, 41: 599-607

[2] ReedJ. C., WilsonD. B.. Cancer immunotherapy targeting survivin. Clin Cancer Res, 2003, 9: 6310-6315

[3] SledzC. A., WilliamsB. R.. RNA interference in biology and disease. Blood, 2005, 106(3): 787-794

[4] GrunwellerA., HartmannR. K.. RNA interference as a gene-specific approach for molecular medicine. Curr Med Chem, 2005, 12(26): 3143-3161

[5] UprichardS. L.. The therapeutic potential of RNA interference. FEBS Lett, 2005, 579(26): 5996-6007

[6] WangY., WangJ. L.. The expression and implication of survivin in primary cancer. Chin Diget J (Chinese), 2002, 22(8): 463-469

[7] ChenJ. G., SongX. M.. Estimation and analysis of the development of liver cander in China. Tumor Chin (Chinese), 2005, 14(1): 28-31

[8] LiF.. Role of survivin and its splice variants in tumori-genesis. Br J Cancer, 2005, 31;92(2): 212-216

[9] ZaffaroniN., PennatiM., DaidoneM. G.. Survivin as a target for new anticancer interventions. J Cell Mol Med, 2005, 9(2): 360-372

[10] GrossmanD., KimP. J., Blanc-BrudeO. P., et al.. Transgenic expression of survivin in keratinocytes counteracts UVB-induced apoptosis and cooperates with loss of P53. J Clin Invest, 2001, 108: 991-999

[11] ShankarS. L., ManiS., OguinK.N., et al.. Survivin inhibition induces human neural tumor cell death through cas-pase-independent and dependent pathways. J Neurochem, 2001, 79: 426-436

[12] WheatleyS. P., McNeishI. A.. Survivin: a protein with dual roles in mitosis and apoptosis. Int Rev Cytol, 2005, 247: 35-88

[13] SchimmerA. D.. Inhibitor of apoptosis proteins: translating basic knowledge into clinical practice. Cancer Res, 2004, 15;64(20): 7183-7190

[14] Zangemeister-WittkeU., SimonH. U.. An IAP in action: the multiple roles of survivin in differentiation, immunity and malignancy. Cell Cycle, 2004, 3(9): 1121-1123