Zhang Yue Ying, Wu Li Cun, Wang Zhao Peng, Wang Zhao Xia, Jia Qing, Jiang Guo Sheng, Zhang Wei Dong
Key laboratory for Modern Medicine and Technology of Shandong Province, Institute of Basic Medicine, Shandong Academy of Medical Science, Jinan, China;
J Clin Med Res. 2009 Apr;1(1):24-31. doi: 10.4021/jocmr2009.01.1220. Epub 2009 Mar 24.
Prostate cancer is a major cause of cancer-related death in men. Therefore there has been considerable interest to explore neoadjuvant therapy. Polypeptide extracted from scorpion venom (PESV), originally obtained from the East-Asian scorpion Buthus martensi Karsch (BmK), is being studied for both prevention and treatment of various human malignancies including prostate cancer.
The present study was to investigate the effect of PESV on cell proliferation, cell cycle, and apoptosis in human androgen-independent prostate cancer cells DU-145 in vitro.
PESV treatment on these cells resulted in a significantly dose-dependent growth inhibition with a G1 phase arrest at 40μg/mL after 48h treatment. PESV treatment strongly induced expression of p27 (Kip1), but resulted in a decrease in cyclin E, one of cyclins involved in G1 progression. In other studies, PESV treatment also induced high apoptosis index (AI), confirmed by TdTmediated dUTP-biotin nick-end labeling (TUNEL) assay. Further, the apoptosis induction by PESV (40μg/mL) in DU145 cells was associated with an increase of pro-apoptotic protein Bax.
These results suggest that PESV modulates the expression of cell cycle-related and apoptosis-related proteins and induces growth inhibition and apoptosis of DU145 cells, providing a strong rationale for future studies to evaluate prevention or/and intervention strategies for PESV in pre-clinical prostate cancer models.
Prostate cancer, PESV, cell proliferation, cell cycle, apoptosis.
前列腺癌是男性癌症相关死亡的主要原因。因此,探索新辅助治疗引起了人们的广泛关注。从蝎毒中提取的多肽(PESV)最初从东亚蝎子东亚钳蝎(BmK)中获得,目前正在研究其对包括前列腺癌在内的各种人类恶性肿瘤的预防和治疗作用。
本研究旨在体外研究PESV对人雄激素非依赖性前列腺癌细胞DU - 145的细胞增殖、细胞周期和凋亡的影响。
用PESV处理这些细胞导致显著的剂量依赖性生长抑制,在48小时处理后,40μg/mL时细胞周期停滞于G1期。PESV处理强烈诱导p27(Kip1)的表达,但导致细胞周期蛋白E(参与G1期进程的细胞周期蛋白之一)减少。在其他研究中,PESV处理还诱导了高凋亡指数(AI),通过TdT介导的dUTP - 生物素缺口末端标记(TUNEL)试验得以证实。此外,PESV(40μg/mL)诱导DU145细胞凋亡与促凋亡蛋白Bax的增加有关。
这些结果表明,PESV调节细胞周期相关蛋白和凋亡相关蛋白的表达,诱导DU145细胞的生长抑制和凋亡,为未来在临床前前列腺癌模型中评估PESV的预防或/和干预策略的研究提供了有力依据。
前列腺癌;PESV;细胞增殖;细胞周期;凋亡