Resveratrol inhibits DHT-induced progression of prostate cancer cell line through interfering with the AR and CXCR4 pathway
Resveratrol inhibits DHT-induced progression of prostate cancer cell line through interfering with the AR and CXCR4 pathway
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DOI：
10.1016/j.jsbmb.2019.105406
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发表时间：
2019-09-01
影响因子：
4.1
通讯作者：
Choi, Kyung-Chul
中科院分区：
文献类型：
--
作者：
Jang, Yin-Gi;Go, Ryu-Eun;Choi, Kyung-Chul
前列腺癌（PCa）是世界范围内男性中最常见的恶性肿瘤之一和癌症相关死亡的第二大常见原因，并且已知其通过雄激素受体（AR）受到双氢睾酮（DHT）作用的影响。白藜芦醇（Resveratrol，Res）是葡萄和红酒中的一种植物化学物质，具有抗炎、抗氧化、抗癌等多种生物学作用。CXCR 4作为一种趋化因子受体已被发现在癌症转移中上调，并已被用作各种类型癌症的预后标志物，包括白血病、乳腺癌和前列腺癌。在这项研究中，我们重点研究了DHT通过影响AR和CXCR 4通路在诱导前列腺癌进展中的作用。此外，我们研究了白藜芦醇对DHT诱导的前列腺癌转移的抑制作用。在细胞活力测定中，DHT提高了LNCaP前列腺癌细胞的细胞活力，另一方面，Res及其与作为AR拮抗剂的比卡鲁胺（BCT）或作为CXCR 4抑制剂的AMD 3100的组合显著降低了由DHT促进的细胞活力。跨孔迁移试验和伤口愈合试验与细胞活力试验结果相似。Western blot分析结果显示，Res处理后AR、CXCR 4、p-PI 3 K、Res及其与BCT或AMD 3100联合应用可降低p-AKT及其下游与细胞周期进程和上皮-间质转化（EMT）相关基因的表达，增加凋亡相关基因的表达。本研究提示，Res及其与AR和CXCR 4拮抗剂的联合应用可用于抑制前列腺癌的转移行为。
Prostate cancer (PCa) is one of the most common malignancies and the second most common cause of cancer-related deaths in men world-wide and is known to be affected by the action of dihydrotestosterone (DHT) via androgen receptor (AR). Resveratrol (Res) as a phytochemical in grapes and red wine has diverse biological effects such as anti-inflammation, anti-oxidation and anti-cancer. CXCR4 as a chemokine receptor has been found to be upregulated in cancer metastasis and has been used as a prognostic marker in various types of cancer, including leukemia, breast cancer, and prostate cancer. In this study, we focused on the role of DHT in the induction of prostate cancer progression by affecting the AR and CXCR4 pathway. Also, we investigated the inhibition effect of resveratrol on DHT-induced prostate cancer metastasis. In cell viability assay, DHT increased the cell viability of LNCaP prostate cancer cells, on the other hand, Res and its combination with bicalutamide (BCT) as an AR-antagonist or AMD3100 as a CXCR4 inhibitor significantly reduced the cell viability promoted by DHT. Trans-well migration assay and wound healing assay represented the similar results with cell viability assay. According to the results of TUNEL assay, the apoptotic activity was induced by treatment of Res. As results of western blot analysis, the expression of AR, CXCR4, p-PI3K, and p-AKT and the downstream genes related with cell cycle progression and epithelial-mesenchymal transition (EMT) were decreased and the expression of the apoptosis-related genes was increased by treatment of Res and its combination with BCT or AMD3100. This study would suggest that Res and its combination with AR and CXCR4 antagonists can be used in order to suppress the metastatic behaviors of prostate cancer.