川楝素对人卵巢癌细胞侵袭和迁移的影响

Effect of toosendanin on invasion and migration of human ovarian cancer cells

目的:探讨川楝素(toosendanin,TSN)对人卵巢癌细胞迁移和侵袭能力的影响及相关机制。方法:用不同浓度川楝素处理人卵巢癌CAVO-3和SKVO-3细胞,采用CCK-8法检测TSN处理12、24、48、72和96 h后的细胞存活率;通过细胞划痕实验和Transwell小室侵袭实验检测TSN对人卵巢癌细胞的迁移和侵袭能力的影响;采用Western blot法检测核因子κB(NF-κB)p65、上皮型钙黏蛋白(E-cadherin)、神经型钙黏蛋白(N-cadherin)、波形蛋白(vimentin)和Snail蛋白的表达情况。结果:TSN抑制CAVO-3和SKVO-3细胞活力(P<0.05)。与对照组相比,TSN组CAVO-3细胞的迁移和侵袭能力明显降低,且NF-κB p65和E-cadherin表达升高,N-cadherin、vimentin和Snail表达下降(P<0.05);而加入NF-κB抑制剂BAY11-7082至TSN处理的细胞后明显逆转了以上效应,与TSN组相比,TSN+BAY11-7082组CAVO-3细胞的迁移和侵袭能力显著升高,且E-cadherin表达下降,N-cadherin、vimentin和Snail表达升高(P<0.05)。结论:川楝素能抑制人卵巢癌细胞的迁移和侵袭能力,其机制可能与抑制由NF-κB/Snail信号通路所介导的上皮-间充质转化过程有关。

AIM:To investigate the effect of toosendanin(TSN)on invasion and migration abilities of human ovarian cancer cells and the related mechanism.METHODS:The human ovarian cancer cell lines CAVO-3and SKVO-3were treated with TSN at different concentrations.The cell viabilty at12,24,48,72and96h after TSN treatment was measured by CCK-8assay.Scratch wound healing assay and Transwell assay were employed to measure the invasion and migration abilities of CAVO-3cells.The protein expression of nuclear factor-κB(NF-κB)p65,E-cadherin,N-cadherin,vimentin and Snail was determined by Western blot.RESULTS:TSN significantly inhibited the viability of CAVO-3and SKVO-3cells(P<0.05).Compared with control group,the migration and invasion abilities of CAVO-3cells in TSN group decreased significantly(P<0.05).In addition,the expression of NF-κB p65and E-cadherin protein increased notably,followed with N-cadherin,vimentin and Snail protein decreased significantly(P<0.05).However,the inhibitor of NF-κB BAY11-7082reversed the impact above.Compared with TSN group,the migration and invasion abilities in TSN+BAY11-7082group increased significantly(P<0.05).The protein expression of E-cadherin also decreased notably,followed with the protein expression of N-cadherin,vimentin and Snail increased significantly(P<0.05).CONCLUSION:TSN inhibits the invasion and migration abilities of human ovarian cancer cells,which is related to the inhibition of epithelial-mesenchymal transition process mediated by NF-κB/Snail signaling pathway.