罗格列酮对人胃癌细胞系迁移侵袭的抑制及其机制

Rosiglitazone inhibits cell invasion and metastasis in human gastric cancer cell lines SGC7901 and SGC7901/VCR

目的:探讨罗格列酮对人胃癌SGC7901、SGC7901/VCR细胞侵袭转移能力及LIMK1基因蛋白表达的影响.方法:罗格列酮(40mg/L)作用SGC7901和SGC7901/VCR细胞24h后,采用划痕实验和Transwell实验分别观察罗格列酮对细胞的迁移和侵袭能力.RT-PCR检测LIMK1mRNA和cofilin-1mRNA的表达情况;Westernblot检测LIMK1和p-cofilin-1的蛋白表达.结果:结果显示,40mg/L罗格列酮分别作用SGC7901细胞和SGC7901/VCR细胞24h后,细胞的迁移和侵袭能力均被罗格列酮抑制(P<0.05).RT-PCR结果显示LIMK1mRNA水平明显下降(P<0.05),cofilin-1无明显影响(P>0.05).Westernblot检测显示罗格列酮作用SGC7901细胞和SGC7901/VCR细胞24h后,LIMK1和p-cofilin-1蛋白的表达水平下降(P<0.05).结论:罗格列酮可抑制人胃癌SGC7901和SGC7901/VCR细胞迁移与侵袭能力;罗格列酮抗肿瘤细胞迁移与侵袭的机制可能与其下调LIMK1进而抑制cofilin-1的激活相关.

AIM： To investigate the effect of rosiglitazone （ROS） on cell invasion and metastasis in human gastric cancer cell lines SGC7901 and SGC7901/ VCR and to explore possible mechanisms in- volved. METHODS： Wound healing assay and in vitro invasion assay were used to investigate the an- tirnetastatic activities of ROS in SGC7901 and SGC7901/VCR cells. After treating SGC7901 and SGC7901/VCR cells with ROS （40 μmol/L） for 24 h, the mRNA levels of LIMK1 and cofilin-1 were assessed by reverse transcription-poly-rnerase chain reaction （RT-PCR）, and the protein levels of LIMK1, cofilint and p-cofilin-1 were assessed by Western blot. RESULTS： Treatment with ROS at a concen- tration of 40μmol/L for 24 h significantly in- hibited cellular invasion and metastasis （P 〈 0.05）, down-regulated the expression of LIMK1 mRNA and protein and the level of p-cofilin-1 （all P 〈 0.05） but showed no significant impact on cofilin-l-1 rnRNA level （P 〉 0.05）. CONCLUSION： ROS elicited a significant inhi- bition of in vitro cell migration and invasion in human gastric cancer cell lines SGC7901 and SGC7901/VCR possibly by down-regulating the expression of LIMK1 and inhibiting cofilin-1 ac- tivation.