水通道蛋白抑制剂乙酰唑胺抑制人结肠癌裸鼠移植瘤生长的实验性研究

Effects of aquaporin protein inhibitor acetazolamide on xenograft tumor growth of colon cancer in nude mice

目的研究水通道蛋白抑制剂乙酰唑胺抑制人结肠癌裸鼠移植瘤的生长及其作用机制。方法建立人结肠癌裸鼠移植瘤模型,分为实验组和对照组,实验组给予乙酰唑胺40mg/(kg·d)灌胃给药,对照组灌胃给予同体积灭菌蒸馏水,定期测量肿瘤结节的长、短径。给药21d后,观察治疗效果。同时,采用Westernblot、RT-PCR技术分析两组肿瘤组织中水通道蛋白-1蛋白和mRNA的表达变化。结果乙酰唑胺40mg/(kg·d)灌胃给药治疗人结肠癌裸鼠移植瘤,明显抑制了肿瘤的生长,肿瘤抑制率为88.28%。实验组与对照组相比,水通道蛋白-1蛋白和mRNA的表达明显减少(P<0.01)。结论水通道蛋白抑制剂乙酰唑胺通过抑制水通道蛋白-1抑制人结肠癌裸鼠移植瘤的生长。

[Objective]To study the effects of aquaporin protein inhibitor acetazolamide on xenograft tumor growth of colon cancer in nude mice and its mechanisms. [Methods]Establishing human colon cancer model in nude mice, mice were randomly divided into two groups： experimental group and control group. Acetazolamide was given at a volume of 0.1 mL per mice [40 mg/（kg·d）, ig] in experimental group, the same volume of sterile saline was given in control group （ig）. The major axis and minor axis of the tumour were measured regularly. After 21 days, observe the treatment effect. The protein and m-RNA level of AQP-1 in tumor tissues from two groups was investigated respectively by Western blot, RT-PCR methods. [Results] Acetazolamide [40 mg/（kg·d）, ig] significantly inhibite the xenograft tumor growth of colon cancer in nude mice.The inhibition rate was 88.28%. In comparison with the control group, AQP-1 protein and mRNA level was significantly reduced in the experimental group （P 0.01）. [Conclusion]Acetazolamide can suppress the xenograft tumor growth by inhibiting AQP-1 expression, and the mechanisms remain to be explored in detail.