Abstract
Several studies have shown that transient receptor potential cation channel subfamily M member 8 (TRPM8), which has been regarded as a novel prostate-specific marker, serves a key role in processes such as the proliferation, viability and cell migration of prostate cancer cells. Efforts have been made to uncover the potential role of targeting TRPM8 in the management of prostate cancer; it has been verified that TRPM8-targeted blockade, either by RNA interference-mediated depletion or specific TRPM8 inhibitors, could reduce the rate of proliferation and proliferative fraction, and induce apoptosis in prostate cancer cells. The aim of the present study was to investigate the effect of knockdown of TRPM8 on chemosensitivity in prostate cancer LNCaP and PC3 cells. The RNA interference-mediated depletion of TRPM8 inhibited proliferation and enhanced epirubicin chemosensitivity of LNCaP and PC3 cells, and promoted epirubicin-induced apoptosis by increasing the phosphorylation of p38 mitogen-activated protein kinase (hereafter p38) and c-Jun N-terminal kinase (JNK)/mitogen-activated protein kinase signaling pathways, which was demonstrated via the use of specific inhibitors of phosphorylation of p38 and JNK. The results demonstrate that the targeted silencing of TRPM8 expression is a therapeutic strategy for treatment of prostate cancer that has considerable potential, even for castration-resistant prostate cancer.
Highlights
Prostate cancer (PCa) is one of the leading threats to men's health, accounting for 25% of incident cases of cancer diagnosed in adult males in the United States annually, and ~9% of incidences of cancer‐associated mortality in the same population, according to statistical data from 2016 [1]
The present study reports evidence that the knockdown of TRPM8 enhanced the chemosensitivity of prostate cancer cells to EPI, which would indicate the potential of a targeted TRPM8‐silencing therapeutic strategy to cure of PCa
Cells were incubated with vehicle (0.01% DMSO) or different concentrations (0, 200, 400, 600, 800, 1,000 ng/ml) of EPI for 48 h by CCK‐8 assay, and are expressed as percentages relative to the control, which was taken as 100%, and treated with medium‐containing vehicle (0.01% DMSO). *P
Summary
Prostate cancer (PCa) is one of the leading threats to men's health, accounting for 25% of incident cases of cancer diagnosed in adult males in the United States annually, and ~9% of incidences of cancer‐associated mortality in the same population, according to statistical data from 2016 [1]. PCa cells are considered to depend on androgens for survival and growth in its early stages [2], and androgen ablation therapy may be a sensitive and effective way of reducing tumor growth; the treatment options for the late‐stage disease termed castration‐resistant prostate cancer (CRPC), remain relatively inefficient [3], as CRPC responds poorly to chemotherapy [4]. Epirubicin (EPI) has been repeatedly found to exhibit activity as a cytotoxic agent for prostate cancer patients, either administered alone or in combination; drug resistance often leads to treatment failure in CRPC patients [5]. As a non‐selective Ca2+‐permeable cation channel, transient receptor potential cation channel subfamily M member 8 (TRPM8) serves a key role in Ca2+ homoeostasis, which is one of the vital factors in cancer‐associated cell signaling pathways. TRPM8 has emerged as a promising prognostic marker and putative therapeutic target in PCa for its vital
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