目的:探讨去甲斑蝥素对环氧合酶-2(COX-2)过表达人肠癌移植瘤裸鼠模型的抑制作用。方法:建立COX-2过表达的人肠癌移植瘤裸鼠模型,观察去甲斑蝥素(NCTD)对瘤体生长、裸鼠生存期和COX-2表达的影响。结果:成功建立COX-2过表达的移植瘤裸鼠模型,且HCT-116/COX-2实验组中COX-2蛋白表达显著上调,与对照组比较具有统计学差异(P〈0.05);HCT-116/COX-2组的瘤体生长速度明显高于HCT-116组及空质粒组,差异有统计学意义(P〈0.05);COX-2过表达组生存天数明显少于HCT-116组和空质粒组,差异有统计学差异(P〈0.05);NCTD对COX-2过表达裸鼠瘤体生长有明显的抑制作用,并且呈剂量依赖性;NCTD低剂量组、中剂量组、高剂量组裸鼠平均生存天数分别为(80.6±6.9)、(92.8±16.5)、(93.4±14.5)d,与HCT-116-COX-2(75.7±11.2)d比较均有统计学差异(P〈0.05);NCTD对COX-2的表达有明显抑制作用,且呈剂量依赖性。结论:COX-2对人结肠癌裸鼠移植瘤的生长有明显的促进作用,且降低了裸鼠的生存期;NCTD能够抑制裸鼠移植瘤的生长,呈现剂量依赖性,并能延长荷瘤裸鼠的生存期,可能通过降低COX-2的表达抑制裸鼠结肠癌的生长。
Objective: To investigate the effects of norcantharidin on xenografts tumor nude mice of human colorectal cancer with COX-2 over-expression,for providing experimental evidence of traditional Chinese medicine on prevention and treatment in colorectal cancer.Methods: Establishing xenografts tumor nude mice model of human colorectal cancer with COX-2 over-expression,to observe the effect of norcantharidin on tumor growth,survival time of nude mice and COX-2 expression.Results: Successfully established xenografts tumor nude mice model of human colorectal cancer with COX-2 over-expression.Compared with the model group,COX-2 protein expression in HCT-116/COX-2 group was significantly up-regulated,the difference was statistically significance(P0.05);tumor growth rate in HCT-116/COX-2 group was significantly higher than the HCT-116 group and empty plasmid group,the difference was statistically significance(P0.05);survival time of COX-2 over-expression group was significantly less than the HCT-116 group and the empty plasmid group with statistical significance(P0.05);Norcantharidin significantly inhibited the tumor growth in nude mice with COX-2 over-expression in a dose-dependent manner;the average survival days of nude mice with COX-2 over-expression was 75.7±11.2,but the norcantharidin groups with different doses were(80.6±6.9) days,(92.8±16.5) days,(93.4±14.5) days from the low dose group to the middle dose group and high dose groups,which were all statistically significant compared with HCT-116/COX-2 group(P0.05);norcantharidin could significantly inhibited the COX-2 expression in a dose-dependent manner.Conclusion: COX-2 significantly promoted the growth of xenografts tumor in nude mice,and reduced the survival time of nude mice;norcantharidin could inhibit the growth of xenografts tumor in nude mice in a dose-dependent manner,and extend the survival time of nude mice.Norcantharidin might inhibit tumor growth by inhibiting the expression of COX-2.