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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 effect of gabexate mesylate on the proliferation of human pancreatic cancer BxPC-3 cells and the growth of xenografts in nude mice. Methods: The cell growth inhibition rates of BxPC-3 cells after treated with 0, 0.01, 0.1, 0.25, 0.5 and 1.0 mmol / L LGM for 24, 48 and 72 h respectively were detected by cell counting method. Flow cytometry The apoptotic rates of BxPC-3 cells were determined by RT-PCR and Western blotting. The apoptotic rate of BxPC-3 cells was determined after 24h / mmol / L LGM treatment. The pancreatic cancer xenografts model was established and divided into experimental group (GM5mg / kg) and control group (0.9% sodium chloride solution) The tumors were inoculated intraperitoneally 1 day after inoculation of tumor tissue, twice a day for 14 days. The tumor size of two groups of nude mice was measured weekly for 6 weeks. The tumor inhibition rate was calculated. Results: Compared with non-administration, GM had no inhibitory effect on the growth of BxPC-3 cells at the concentration of 0.01 and 0.1 mmol / L (P> 0.05) (P <0.05) in a dose and time dependent manner. The apoptotic rates of BxPC-3 cells after treated with 0.25, 0.5 and 1.0 mmol / L of LG were 7%, 15.2% and 21.4% (P <0.05 or P <0.01). Compared with the control group, there was no significant difference in the volume of tumor mass in the experimental group within 2 weeks after administration (P> 0.05) (P <0.05). The inhibition rate of GM on nude mice transplanted tumor was 41.43%. Conclusion: GM can significantly inhibit the growth of BxPC-3 cells and induce apoptosis of the cells in a dose and time-dependent manner. It can effectively inhibit the growth of allograft xenografts in nude mice.