Home Neoplasma 2017 Neoplasma Vol.64, No.5, p.709-717, 2017

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Founded: 1954
ISSN 0028-2685
ISSN 1338-4317 (online)

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Neoplasma Vol.64, No.5, p.709-717, 2017

Title: Knockdown of CFTR enhances sensitivity of prostate cancer cells to cisplatin via inhibition of autophagy
Author: Q. Zhu, H. Li, Y. Liu, L. Jiang

Abstract: Prostate cancer is one of the most lethal diseases in men worldwide. Although the survival rate of men diagnosed with prostate cancer has increased with the improvement of treatments, drug resistance still remains a big challenge for improving overall survival. Cystic fibrosis transmembrane conductance regulator (CFTR), a cAMP-activated anion channel, has been reported to have a pivotal role in the pathogenesis of various cancers, but its role in chemoresistance of prostate cancer cells is poorly understood. In our study, we found that CFTR expression was significantly increased in prostate cancer tissues associated the chemoresistance, and in the cisplatin-resistant cell line LNCaP/CP compared with their respective parental cells. Cisplatin treatment inhibited CFTR expression in a concentration-dependent manner, which was correlated with a decrease in cell viability. Moreover, inhibition of CFTR by transfection of small interfering RNA enhanced cisplatin-induced the decrease of cell viability. Autophagy was dramatically increased in LNCaP/CP cells, as evidenced by autopaphgic markers as well as fluorescence microscopy analysis of GFP-LC3, MDC and AO staining. Of note, inhibiting autophagy by 3MA induced LNCaP/CP cell apoptosis, showed by MTT assay and Hoechst 33258 staining. In addition, blockade of CFTR also inhibited LNCaP/CP cell viability and autophagy. Furthermore, the dephosphorylation of AKT and mTOR was reversed by CFTR inhibition, indicating the knockdown of CFTR might inhibit autophagy in LNCaP/CP cells via activation of AKT/mTOR signaling. Altogether, these results provide a novel understanding of the mechanism for acquired cisplatin. Inhibition of CFTR may be a useful strategy to increase the efficacy of cisplatin to treat prostate cancer by preventing the protective response of autophagy.

Keywords: cisplatin, chemoresistance, prostate cancer, autophagy, CFTR
Published online: 31-Aug-2017
Year: 2017, Volume: 64, Issue: 5 Page From: 709, Page To: 717

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