甲磺酸加贝酯对人胰腺癌BxPC-3细胞增殖及其裸鼠移植瘤生长的抑制作用

Inhibitory Effects of Gabexate Mesylate on the Proliferation of Human Pancreatic Cancer BxPC-3 Cells and the Growth of Transplantable Tumor in Nude Rats

目的:研究甲磺酸加贝酯(GM)对人胰腺癌BxPC-3细胞增殖及其裸鼠移植瘤生长的抑制作用。方法:采用细胞计数法检测0、0.01、0.1、0.25、0.5、1.0mmol/LGM分别作用24、48、72h后BxPC-3细胞的生长抑制率;流式细胞术观察0、0.25、0.5、1.0mmol/LGM作用24h后BxPC-3细胞的凋亡率;建立胰腺癌裸鼠移植瘤模型,随机分为实验(GM5mg/kg)组和对照(0.9%氯化钠溶液)组,每组7只,于接种瘤组织后1d腹腔注射相应药物,每日2次,连续14d,每周测量两组裸鼠肿瘤大小,连续测量6周,计算抑瘤率。结果:与未给药比较,GM在0.01、0.1mmol/L浓度时对BxPC-3细胞的生长没有抑制作用(P>0.05),在0.25、0.5、1.0mmol/L浓度时对BxPC-3细胞的生长抑制率明显增加(P<0.05),且呈剂量和时间依赖性;0.25、0.5、1.0mmol/LGM作用后BxPC-3细胞的凋亡率分别为7%、15.2%、21.4%,明显高于未给药的2%(P<0.05或P<0.01);与对照组比较,实验组大鼠瘤块体积在给药2周内差异无统计学意义(P>0.05),从第3周开始明显减小(P<0.05),GM对裸鼠移植瘤的抑瘤率为41.43%。结论:GM可明显抑制BxPC-3细胞的生长,并诱导该细胞凋亡,呈剂量和时间依赖性;可有效抑制裸鼠异体移植瘤的生长。

OBJECTIVE： To study the inhibitory effects of gabexate mesylate （GM） on the proliferation of human pancreatic cancer BxPC-3 cells and the growth of transplantable tumor ih nude rats. METHODS： The inhibitory rates of 0, 0.01, 0.1, 0.25, 0.5 and 1.0 mmol/L GM on the growth of BxPC-3 cells were detected by cytometry after treated for 24, 48 and 72 h, respectively. Apoptosis rates of BxPC-3 cells were detected by flow cytometry after treated with 0, 0.25, 0.5 and 1.0 mmol/L GM for 24 h. The transplantable tumor model of nude rats was established and randomly divided into trial group （GM 5 mg/kg） and control group （0.9% sodium chloride） with 7 rats in each group. A day after inoculated with tumor tissues, both groups were given relevant medicines intraperitoneally twice a day for consecutive 14 days. The size of tumor in nude rats was determined in 2 groups each week, and anti-tumor rate was calculated after consecutive 6 weeks of measurement. RESULTS： Compared with non-administration, 0.01 and 0.1 mmol/L GM had no inhibitory effect on the growth of BxPC-3 cells （P〉0.05） ; the inhibitory effect of 0.25, 0.5 and 1.0 mmol/L GM on the growth of BxPC-3 cells were increased significantly （P〈0.05）, in dose-dependent and time-dependent manner. The apoptotic rates of BxPC-3 cells were 7%, 15.2% and 21.4% after treated with 0.25, 0.5, 1.0 mmol/L GM, which were signifi- cant higher than 2% of BxPC-3 cells without treatment （P〈0.05 or P〈0.01）. Compared with control group, there was no statisti- cal significance in the tumor volume of rats in trial group within 2 weeks of treatment （P〉0.05）, but the tumor volume of rats de- creased significantly since third week （P〈0.05）. Anti-tumor rate of GM in nude rats was 41.43%. CONCLUSIONS： GM can inhibit the growth of BxPC-3 cells and induce the apoptosis of the cells in dose-dependant and time-dependant manner. It also can in- hibite the growth of transplantable tumor in unde rats.