Artesunate Suppresses the Growth of Prostatic Cancer Cells through Inhibiting Androgen Receptor
Artesunate Suppresses the Growth of Prostatic Cancer Cells through Inhibiting Androgen Receptor
复制标题
青蒿琥酯通过抑制雄激素受体抑制前列腺癌细胞的生长
DOI：
10.1248/bpb.b16-00908
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发表时间：
2017-04-01
影响因子：
2
通讯作者：
Wang, Shou-Lin
中科院分区：
文献类型：
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作者：
Wang, Zhenzhong;Wang, Chao;Wang, Shou-Lin
前列腺癌（Prostatic cancer，PCa）是男性癌症相关死亡的主要原因，通常被认为是一种雄激素敏感性癌症。青蒿琥酯（ART）是一种半合成的中药青蒿衍生物，就是这样一种抗癌剂。然而，ART对PCa细胞的作用和机制尚不清楚。本研究旨在阐明雄激素受体（AR）参与青蒿琥酯（ART）抗前列腺癌（PCa）作用的机制。分别采用MTT法和TUNEL法检测PCa细胞22 rv 1的存活率和凋亡率。在AR或DNMT 3b过表达或干扰的细胞中检测到AR和DNMT的异位表达。ART剂量依赖性地抑制肿瘤生长，抑制细胞活力，增强细胞凋亡，减少AR表达，并增加DNMT 3b的表达和在移植小鼠或体外的22 rv 1细胞中的催化活性。AR下调DNMT 3b的表达，过表达AR或干扰DNMT 3b可逆转ART诱导的22 rv 1细胞毒性和凋亡，而过表达DNMT 3b不能改变ART对22 rv 1细胞的作用。结果表明，ART通过AR-DNMT 3b途径抑制前列腺癌细胞的肿瘤生长，潜在的ART将允许利用这种中国治疗剂用于前列腺癌的潜在治疗。
Prostatic cancer (PCa) is a leading cause of cancer related death in males and is often regarded as a kind of androgen-sensitive cancer. Artesunate (ART), a semi-synthetic derivative of the Chinese herb Artemisia annua, is such an anti-cancer agent. However, the effects and mechanism of ART on PCa cells remains unclear. The study aims to elaborate the mechanism of the involvement of androgen receptor (AR) in anti-prostatic cancer (PCa) of artesunate (ART). PCa cells 22rv1 were used in vivo and in vitro, and the viability and apoptosis were conducted using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) assay, respectively. Ectopic expressions of AR and DNA methyltransferase (DNMT) were detected in cells in overexpression or interference of AR or DNMT3b. ART dose-dependently suppressed tumor growth, inhibited cell viability, enhanced apoptosis, decreased AR expression, and increased the expression and the catalytic activity of DNMT3b in 22rv1 cells either in transplanted mice or in vitro. Furthermore, AR downregulated DNMT3b expression, and overexpression of AR or interference of DNMT3b could reverse ART-induced cytotoxicity and apoptosis in 22rvl cells, whereas overexpression of DNMT3b could not change the effect profiles of ART on the cells. The results indicated that ART suppressed tumor growth of prostatic cancer cells through AR-DNMT3b pathway, underlying ART will allow for the utilization of this Chinese therapeutic agent for the potential treatment of prostate cancer.