Mutant K-ras specific siRNA inhibits proliferation, migration and induces apoptosis of lung cancer A549 cells

doi:10.3872/j.issn.1007-385X.2009.6.003

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Archive > Volume 16 Issue 6 > 2009,16(6):564-569. DOI:10.3872/j.issn.1007-385X.2009.6.003 Prev Next

Monographic Report

Mutant K-ras specific siRNA inhibits proliferation, migration and induces apoptosis of lung cancer A549 cells

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Abstract:

Objective:To construct Krastargeted siRNAs (Kras siRNA) and to investigate the inhibitory effects of Kras siRNAs on the growth and migration of lung cancer A549 cells (containing mutant Kras gene) and NCIH446 cells (containing wildtype Kras gene). :Methods: :Four Kras siRNAs (Kras siRNA1~Kras siRNA3 targeting wildtype Kras and Kras siRNA4 targeting mutant Kras) were designed and artificially synthesized; they were used to transfect A549 cells and NCIH446 cells. The expressions of Ras mRNA and protein were examined by RTPCR and Western blotting. The inhibitory effects of Kras siRNAs on the proliferations of A549 and NCIH446 cells were determined by MTT assay. The effects of Kras siRNAs on the cell migration and apoptosis were observed by Transwell assay and Hoechst 33258 staining, respectively. :Results: :Mutant Krastargeted siRNA (Kras siRNA4) specifically inhibited the Kras expression but had no influence on Hras and Nras expression in A549 cells. Kras siRNA4 inhibited the proliferation of A549 cells but did not inhibit that of NCIH446 cells, which contained wild type Kras gene. Kras siRNA4 also induced apoptosis and inhibited migration of A549 cells. :Conclusion: :Mutant Krastargeted siRNA4 can inhibit the proliferation, migration and induce apoptosis of A549 cells. It may be a potential and personalized drug for the treatment against lung cancer containing mutant Kras gene.

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Supported by the National HighTechnology Research and Development Program of China (No. 2008AA02Z135); the Development and Reform Commission Program of Fujian Province (2008, the Third Batch, No. 26)

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