Cathepsin L-mediated resistance of paclitaxel and cisplatin is mediated by distinct regulatory mechanisms.

ABSTRACT:

Background

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.

Methods

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.

Results

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-

SUBMITTER: Zhao Y 

PROVIDER: S-EPMC6670178 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature