[RNA interference targeting focal adhesion kinase inhibited the growth of human hepatocellular carcinoma sk-hep-1].

Sichuan Da Xue Xue Bao Yi Xue Ban

State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China.

Published: July 2011

Objective: To test the impact of silencing focal adhesion kinase (FAK) gene on human hepatocellular carcinoma cell line sk-hep-1 using RNA interference (RNAi) in vitro, and its therapeutic effect on human hepatocellular carcinoma xenograft in vivo.

Methods: The plasmids generating short hairpin RNA that target FAK gene were transfected into sk-hep-1 cell line through Fugene HD. The impact was analyzed using flow cytometry, RT-PCR and western bolt. Human hepatocellular carcinoma xenograft in nude mice was established and treated with injection of the plasmids that packaged by cationic liposome into the tail veins the mice. The volumes and weights of the tumors were measured. The tumor tissues were analysed with FAK, CD31 and PCNA immunohistochemistry and TUNEL.

Results: The RNAi targeting FAK significantly down regulated the expression of FAK in mRNA and the level of protein (P < 0.001), and increased the cell apoptosis in vitro. The mice treated with pshFAK had slower tumor growth, resulting in smaller tumor size and lower tumor weight (P < 0.001) comparing to the controls. Decrease in FAK protein expression, tumor angiogenesis and proliferation, and increase in tumor apoptosis were found in the mice treated with pshFAK compared to the controls (P < 0.001).

Conclusion: The shRNA targeting FAK suppresses the FAK expression of human hepatocellular carcinoma cells sk-hep-1, inhibits tumor growth, and promotes cell apoptosis in vitro and in vivo. FAK could become a candidate target for liver cancer treatment.

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