Affiliation:
1. Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
2. Department of Pediatric Surgery, Maternity and Child Health Hospital of Chongqing Hechuan, Chongqing, China
3. Department of Urology, People’s Hospital of Chongqing Hechuan, Chongqing, China
Abstract
Background: Paclitaxel resistance is the major clinical obstacle in the chemotherapy of prostate cancer (PCa), but the resistant mechanism is less investigated. Purpose: To establish two paclitaxel-resistant PCa cells, provide a comprehensive gene expression profile analysis of resistant cells and the potential target to reverse resistance. Methods: Two Paclitaxel-resistant PCa cells (PC3/PR, LNcap/PR) were established by gradually increasing drug concentration. MTT and transwell assays were performed to detect drug sensitivity, cell proliferation and migration abilities. RNA-Sequencing (RNA-seq) and bioinformatic analyses were performed to identify abnormally expressed genes (AEGs) in resistant cells, and annotate the biological functions of AEGs. The role of the candidate AEG, TLR-4, on the resistant phenotypes was further investigated. Results: The resistance index of resistant cells was 2-3, and they showed a slower proliferation and increased migration ability. 4741 AEGs were screened out (Log2fold change absolute: log2FC(abs) > 1) in the resistant cells, and they were enriched in 2'-5'-oligoadenylate synthetase activity and chemical carcinogenesis. A number of AEGs, CCND2, IGFBP3, FOS, SHH, ZEB2, and members of FGF, FGFR and WNT families were also identified to be involved in cancer- and resistant phenotype-related processes. Finally, TLR-4 was validated significantly increased in resistant cells, and knockdown of TLR-4 increased drug-sensitivity, inhibited the proliferation and migration abilities. Conclusions: The study provided a comprehensive gene expression profile of paclitaxel-resistant PCa cells, and TLR-4 could be a potential target to reverse paclitaxel resistance.
Funder
Chongqing Natural Science Foundation
Subject
Health, Toxicology and Mutagenesis,Toxicology,General Medicine
Cited by
2 articles.
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