IDO1抑制剂对肺癌细胞增殖和迁移的影响

Effects of IDO1 Inhibitor on Cell Proliferation and Migration of Lung Cancer

目的研究吲哚胺2,3-双加氧酶1(indoleamine 2,3-dioxygenase 1,IDO1)抑制剂对肺癌细胞增殖、迁移的影响及其相关机制。方法使用不同浓度梯度的IDO1抑制剂处理肺癌细胞A549和H460细胞系,通过细胞毒性和克隆形成实验检测细胞的增殖情况;通过Transwell和划痕愈合实验检测细胞的迁移情况;通过Western blot实验检测上皮间质转化(epithelial-mesenchymal transition,EMT)和铁死亡相关蛋白表达变化情况。结果与对照组对比,IDO1抑制剂组A549和H460细胞增殖和迁移能力明显受到抑制(P均<0.05);在EMT相关蛋白中,Snail、Slug、N-cadherin、Vimentin和基质金属蛋白酶9(matrix metalloproteinase 9,MMP-9)蛋白表达量显著下调,而E-cadherin蛋白表达显著上调(P均<0.05);在铁死亡相关蛋白中,血红素氧合酶1(heme oxygenase 1,HO-1)和转铁蛋白(transferrin,Tf)的蛋白表达显著上调,而铁死亡负调控蛋白(SLC40A1、SLCTA11、GLS、GPX4)表达显著下调(P均<0.05)。结论IDO1抑制剂通过抑制EMT及诱导铁死亡,从而抑制肺癌细胞的增殖和迁移。

Objective To investigate the effects of indoleamine 2,3-dioxygenase 1(IDO1)inhibitor on the proliferation and migration of lung cancer cells and its related mechanisms.Methods Different concentration gradients of IDO1 inhibitor were used to treat A549 and H460 cell lines,cell proliferation was detected by cytotoxicity and clone formation experiments;cell migration was detected by Transwell and scratch healing experiments;and the expression of epithelial-mesenchymal transition(EMT)and ferroptosis-related proteins were detected by Western blot.Results Compared with the control group,the proliferation and migration ability of A549 and H460 cells in the IDO1 inhibitor treatment group were significantly inhibited(all P<0.05).Among EMT-related proteins,the protein expression of Snail,Slug,N-cadherin,Vimentin and matrix metalloproteinase 9(MMP-9)were significantly down-regulated,while the expression of E-cadherin protein was significantly up-regulated(all P<0.05);among the ferroptosis-related proteins,the protein expressions of heme oxygenase 1(HO-1)and transferrin(Tf)were significantly up-regulated,while the negative regulatory proteins of ferroptosis(SLC40A1,SLCTA11,GLS,GPX4)were significantly down-regulated.The inhibitory effects of IDO1 showed a certain degree of dependence on its concentration(all P<0.05).Conclusion IDO1 inhibitor inhibites the proliferation and migration of lung cancer cells by inhibiting EMT and inducing ferroptosis.