蜂毒多肽对膀胱移行细胞癌裸鼠移植瘤生长的影响

Effect of Venom Peptides on the Transplantation Tumor Growth of T24 Bladder Cancer in Nude Mice

目的观察蜂毒多肽对T24膀胱癌细胞增殖、凋亡、细胞侵袭及裸鼠移植瘤生长的影响。方法将1、10、100 mg/ml的蜂毒多肽分别作用于膀胱癌T24细胞12、24和48 h,MTT法检测细胞活力变化及生长抑制率,流式细胞术及Transwell小室法检测蜂毒多肽作用48 h时T24细胞周期、细胞凋亡率及细胞侵袭力。将T24膀胱癌细胞接种于裸鼠,成瘤后分为对照组、蜂毒多肽低剂量组[1 mg/(kg·d)]、中剂量组[5 mg/(kg·d)]和高剂量组[25 mg/kg·d)],检测5、10和15 d裸鼠移植瘤体积、肿瘤生长抑制率及15 d时肝肾功能、血常规变化。结果随蜂毒多肽浓度增加及作用时间延长,T24细胞生长及凋亡发生受到显著影响(P<0.05,P<0.01),100 mg/ml蜂毒多肽作用48 h时,细胞生长抑制率升高,生长周期阻滞于G0/G1期,细胞凋亡率升高,细胞侵袭力显著下降(P<0.01)。蜂毒多肽组裸鼠移植瘤体积显著小于对照组,15 d时蜂毒多肽高剂量组肿瘤体积显著降低(P<0.01)。各组肝肾功能和血常规无明显变化(P>0.05)。结论蜂毒多肽可引起体外T24膀胱癌细胞增殖抑制、凋亡率增加及细胞侵袭力下降,可显著抑制裸鼠膀胱癌细胞移植瘤生长。

Objective To investigate the effect of Venom Peptides on proliferation, apoptosis and invasion of T24 bladder cancer cells and transplantation tumor growth in nude mice. Methods In Venom Peptides groups, 1, 10 and 100 mg/ml of Venom Peptides were respectively applied to bladder cancer T24 cells for 12 h, 24 h and 48 h. Cell vi- ability and growth inhibition rates of T24 cells were detected with MTT methods. Cell cycle, apoptosis rate and cell inva- siveness of T24 cell affected by Venom Peptides for 48 h were detected with flow cytometry and Transwell chamber meth- ods. T24 bladder cancer cells were inoculated into nude mice, and then were divided into control group, small dose of Venom Peptides group （lmg/kg ~ d）, medium dose of Venom Peptides group （5 mg/kg ~ d） and large dose of Venom Peptides group （25mg/kg ~ d ）. Tumor volumes and tumor growth inhibition rates of Venom Peptides at 5 d, 10 d and 15 d were detected, and hepatic and renal functions and changes of routine blood test at 15 d were detected. Results Growth and apoptosis of T24 cells were significantly affected with the increased Venom Peptides concentration and the prolonged action time （P 〈 0.05, P 〈 0.01 ）. In the 100 mg/ml of Venom Peptides group affected for 48h, the cell growth inhibit rate increased, the growth cycle was arrested in G0/G1 phase, the apoptosis rate increased, and the cell invasiveness significantly decreased （P 〈 0. O1 ）. Tumor volumes of the Venom Peptides groups were obviously smaller than that of control group, and the tumor volume of large dose of Venom Peptides group at 15 d significantly decreased （P 〈 0.01 ）. The hepatic and renal functions and routine blood test in all groups showed no significant differences （P 〉 0. 05）. Conclusion Venom Peptides can induce proliferation inhibition, increase of apoptosis rate, decrease of inva- siveness of T24 bladder cancer cells in vitro can significantly inhibit the growth of bladder cancer in nude mice.