Gao Li, Zhang Jing, Liu Xinyan, Zhao Min, Li Lijun, Liu Xin, Zhao Baohua
College of Life Science, Hebei Normal University, Shijiazhuang, China.
Department of Rehabilitation, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China.
Thorac Cancer. 2013 Aug;4(3):306-311. doi: 10.1111/1759-7714.12020.
The aim of this study was to evaluate the cytotoxic and antitumor activity of spider venom (SV).
Cell proliferation and cytotoxicity were determined by H-methyl thymidine incorporation ([ H]-TDR) assay. DNA fragmentation and cell cycle kinetics were analyzed by FACS. In vivo inhibition of tumor size of nude mice by SV (5.0, 10.0, 20.0 mg/kg mice) was constructed.
SV exhibited significant anti-cancer effects on human squamous esophageal carcinoma cells TE13, mainly as a result of cell apoptosis induced by SV. The anti-cancer effects were likely achieved through decreasing [ H]-TdR. TE13 cells treated with SV (25, 50, 100 μg/mL), which were arrested in the G /G phase. SV treatment leads to anti-proliferation effects, and significant apoptosis in TE13 cells with reactive oxygen species (ROS) levels can increase dramatically and decrease cellular mitochondrial membrane potential (MMP). In addition, Western blotting analysis showed that one of the pharmacological mechanisms of SV was to activate the expression of P21. In vivo testing revealed that tumor size was significantly decreased after 21 days of treatment with the venom (P < 0.01).
Our data showed that SVs could inhibit TE13 cell proliferation in vitro and in vivo.
本研究旨在评估蜘蛛毒液(SV)的细胞毒性和抗肿瘤活性。
通过³H-甲基胸腺嘧啶核苷掺入([³H]-TDR)试验测定细胞增殖和细胞毒性。采用流式细胞术分析DNA片段化和细胞周期动力学。构建了SV(5.0、10.0、20.0mg/kg小鼠)对裸鼠肿瘤大小的体内抑制模型。
SV对人食管鳞状癌细胞TE13具有显著的抗癌作用,主要是由于SV诱导细胞凋亡。抗癌作用可能是通过降低[³H]-TdR实现的。用SV(25、50、100μg/mL)处理的TE13细胞停滞于G₂/G₀期。SV处理导致TE13细胞产生抗增殖作用并显著凋亡,同时活性氧(ROS)水平可急剧升高,线粒体膜电位(MMP)降低。此外,蛋白质印迹分析表明,SV的药理机制之一是激活P21的表达。体内试验显示,用毒液处理21天后肿瘤大小显著减小(P<0.01)。
我们的数据表明,SV在体外和体内均可抑制TE13细胞增殖。