Inhibition of ATM reverses EMT and decreases metastatic potential of cisplatin-resistant lung cancer cells through JAK/STAT3/PD-L1 pathway

摘要: The cisplatin-resistance is still a main course for chemotherapy failure of lung cancer patients. Cisplatin-resistant cells own higher malignance and exhibited increased metastatic ability, but the mechanism not clear. In this study, we investigated effects Ataxia Telangiectasia Mutated (ATM) on metastasis. A549CisR H157CisR cell line were generated by long-term treating parental A549 H157 (A549P H157P) with cisplatin. Cell growth, migration invasion determined. Gene expressions determined Western Blot qPCR. Tumor metastasis was using xenograft mouse model. IC50 cisplatin-resistant (A549CisR cells) to cisplatin 6–8 than cells. expressed lower level E-cadherin levels N-cadherin, Vimentin Snail compared A549P H157P cells, stronger capabilities potential ATM expression upregulated in treatment also inhibition specific inhibitor CP466722 or knock-down siRNA suppressed Epithelial-to-Mesenchymal transition (EMT) These data suggest that mediates Expressions JAK1,2,、 STAT3 、PD-L1 could induced Interestedly, PD-L1 via JAK1,2/STAT3 pathway decreased JAK/STAT3 signaling expression. neutralizing Ab reduced EMT invasion. Inhibition inhibitors ATM-induced expression, Importantly, tumor an orthotopic Our results show regulates through activation Overexpression contributes reversed inhibited Thus, may be target cancer.