论文部分内容阅读
Cancer invasion and metastasis, involving a variety of pathological processes andcytophysiological changes,contribute to the high mortality of lung cancer.The type 1 insulin-like growthfactor receptor (IGF-1R),associated with cancer progression and invasion,is a potential anti-invasion andanti-metastasis target in lung cancer.To inhibit the invasive properties of lung cancer cells,we successfullydown-regulated IGF-1R gene expression in A549 human lung cancer cells by small interfering RNA (siRNA)technology,and evaluated its effects on invasion-related gene expression,tumor cell in vitro invasion,andmetastasis in xenograft nude mice.A549 cells transfected with a plasmid expressing hairpin siRNA forIGF-1R showed a significantly decreased IGF-1R expression at the mRNA level as well as the proteinlevel.In biological assays,transfected A549 cells showed a significant reduction of cell-matrix adhesion,migration and invasion.Consistent with these results,we found that down-regulation of IGR-1Rconcomitantly accompanied by a large reduction in invasion-related gene expressions,including MMP-2,MMP-9,u-PA,and IGF-1R specific downstream p-Akt.Direct tail vein injections of plasmid expressinghairpin siRNA for IGF- 1R significantly inhibited the formation of lung metastases in nude mice.Our resultsshowed the therapeutic potential of siRNA as a method for gene therapy in inhibiting lung cancer invasionand metastasis.
Cancer invasion and metastasis, involving a variety of pathological processes andcytophysiological changes, contribute to the high mortality of lung cancer. Type 1 insulin-like growthfactor receptor (IGF-1R), associated with cancer progression and invasion, is a potential anti-invasion and anti-metastasis target in lung cancer. To inhibit the invasive properties of lung cancer cells, we successfully down-regulated IGF-1 R gene expression in A549 human lung cancer cells by small interfering RNA (siRNA) technology, and its its effects on invasion-related gene expression, tumor cell in vitro invasion, andmetastasis in xenograft nude mice. A549 cells transfected with a plasmid expressing hairpin siRNA for IGF-1R showed significantly decreased IGF-1R expression at the mRNA level as well as the proteinlevel. in biological assays, transfected A549 cells showed a significant reduction of cell-matrix adhesion, migration and invasion. Consistent with these results, we found that down-regulation of IGR-1 Rconcomitantly accompanied by a large reduction in invasion-related gene expressions, including MMP-2, MMP-9, u-PA, and IGF-1 R specific downstream p-Akt.Direct tail vein injections of the plasmid expressing hairpin siRNA for IGF- the formation of lung metastases in nude mice. Our resultsshowed the therapeutic potential of siRNA as a method for gene therapy in inhibiting lung cancer invasion and metastasis.