biostudies-literatureZhao YNational Natural Science Foundation of China333https://www.ebi.ac.uk/biostudies/studies/S-EPMC6670178biostudies-literatureUnknown38(1)<h4>Background</h4>Cathepsin L (CTSL) is a cysteine protease known to have important roles in regulating cancer cellular resistance to chemotherapy. However mechanism underlying which regulates CTSL-mediated drug resistance remain largely unknown.<h4>Methods</h4>We used NSCLC cell lines: A549, A549/TAX (paclitaxel-resistant), A549/DDP (cisplatin-resistant), H460 and PC9 cells, to evaluate CTSL and drug resistance changes. Tumor specimens from 53 patients with NSCLC and Xenograft models was also utilized to explore the regulatory relationship of CTSL, TGF-β, Egr-1 and CREB.<h4>Results</h4>TGF-β and smad3 were overexpressed only in A549/TAX cells, silencing TGF-β or smad3 in A549/TAX cells decreased the expression of CTSL and enhanced their sensitivity to paclitaxel. Smad3 binds to the Smad-Journal of experimental & clinical cancer research : CRCathepsin L-mediated resistance of paclitaxel and cisplatin is mediated by distinct regulatory mechanisms.PMC667017881773768817035328157125281671252Xiong YWang AZhu YLin FLiang ZFei YWang WWang YShen XZhao YWang LfalseCathepsin L-mediated resistance of paclitaxel and cisplatin is mediated by distinct regulatory mechanisms.<h4>Background</h4>Cathepsin L (CTSL) is a cysteine protease known to have important roles in regulating cancer cellular resistance to chemotherapy. However mechanism underlying which regulates CTSL-mediated drug resistance remain largely unknown.<h4>Methods</h4>We used NSCLC cell lines: A549, A549/TAX (paclitaxel-resistant), A549/DDP (cisplatin-resistant), H460 and PC9 cells, to evaluate CTSL and drug resistance changes. Tumor specimens from 53 patients with NSCLC and Xenograft models was also utilized to explore the regulatory relationship of CTSL, TGF-β, Egr-1 and CREB.<h4>Results</h4>TGF-β and smad3 were overexpressed only in A549/TAX cells, silencing TGF-β or smad3 in A549/TAX cells decreased the expression of CTSL and enhanced their sensitivity to paclitaxel. Smad3 binds to the Smad-2019-01-01T00:00:00Z2019 Aug2025-04-04T18:37:06.82Z2019-08-28T07:02:23ZS-EPMC66701783137086110.1186/s13046-019-1299-4