柑橘类黄酮诺必擂停对K562裸鼠移植瘤的抑制作用

目的:观察柑橘类黄酮诺必擂停对K562裸鼠移植瘤的抑制作用,探讨其在抑制肿瘤血管生成方面的作用与机制.方法:构建l(562裸鼠移植瘤模型,25只裸鼠分为模型组、诺必擂停低、中、高剂量组和阳性对照组(n=5).造模24 h后分别给与1%羧甲基纤维素钠溶剂、诺必擂停(12.5,25,50 mg·kg~(-1))和环磷酰胺(20 mg·kg~(-1)),连续给药18 d,处死,取肿瘤称重计算抑瘤率;免疫组化法检测药物对肿瘤组织VEGF表达及MVD的影响;鸡胚绒毛尿囊膜实验测定药物对血管新生的作用.结果:诺必擂停可显著抑制K562裸鼠移植瘤的生长,抑瘤率达36%～58%,与模型组比较有显著差异(P<0.01);能显著降低肿瘤组织内微血管生成:诺必擂停低、中、高剂量组CD34表达均低于模型组(中、高剂量组分别P<0.05,P<0.01);抑制VEGF的表达:诺必擂停低、中、高剂量组VEGF均低于模型组(分别P<0.05,P<0.01和P<0.01);抑制CAM血管新生:2,4 μg作用下CAM微血管数显著低于对照组(P<0.01).结论:诺必擂停可以抑制K562裸鼠移植瘤的生长以及肿瘤血管的生成,其作用机制可能与下调肿瘤组织VEGF的表达有关.

Effect of nobiletin on K562 cells xenograft in nude mice

Objective: To observe the inhibitory effect of citrus extract nobiletin on K562 cells xenograft in nude mice and discuss its anticancer activity and mechanism.  Method: The model of K562 cells xenograft was established in nude mice. Twenty-five nude mice were divided to five groups. After 24 hrs of inoculation with K562 tumor cells subcutaneously, 1%CMC-Na in the nude mice of model control group, nobiletin (12.5, 25, 50 mg·kg-1) in the nude mice of nobiletin groups and CTX (20 mg·kg-1) in positive control group were administered once every day. The nude mice were killed at 18th day-point of administration. The inhibitory rate of nobiletin on tumor was calculated according to the measured tumor weight. Immunohistochemistry assay was used to determine the effect of nobiletin on VEGF expression and MVD, and CAM assay was used to detect the effect of nobiletin on vessel regeneration.  Result: Nobiletin have notable inhibition on K562 cells xenograft in nude mice comparing with model control group (P<0.01), the inhibitory rate of nobiletin groups were 36%-58%. The results of immunohistochemical technology showed that the expression of VEGF in nobiletin groups decreased significantly comparing with the model control group (P<0.05, P<0.01, P<0.01). Nobiletin could remarkably decrease the angiogenesis within tumor tissues. The expression of CD34 in nobiletin low dose group and high dose group was lower than that in model control group (P<0.05, P<0.01). The result of CAM indicated that 4 μg and 2 μg nobiletin could inhibit the new blood vessels of CAM (P<0.01).  Conclusion: Nobiletin inhibited the tumor growth and angiogenesis by reducing the VEGF expression of K562 cells xenograft in nude mice.