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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K562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:2,4μg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。
OBJECTIVE: To observe the inhibitory effect of citrus flavonoids on the transplanted tumor of K562 nude mice and its role and mechanism in inhibiting tumor angiogenesis. METHODS: A xenograft model of K562 nude mice was constructed. Twenty-five nude mice were divided into model group, Nobel’s stopping low, middle, high dose group and positive control group (n=5). 24 h after the model was given 1% sodium carboxymethyl cellulose solvent, Nubisidine (12.5, 25, 50 mg.kg-1) and cyclophosphamide (20 mg.kg-1), respectively, for continuous administration On day 18, the rats were sacrificed and tumors were weighed to calculate the tumor inhibition rate. Immunohistochemistry was used to examine the effect of drugs on VEGF expression and MVD in tumor tissues. Chicken chorioallantoic membrane was used to determine the effect of drugs on angiogenesis. RESULTS: Nalbitron can significantly inhibit the growth of transplanted tumors in K562 nude mice, and the tumor inhibition rate was 36% to 58%, which was significantly different from that of the model group (P<0.01). The tumor angiogenesis was significantly reduced: The expression of CD34 in the low-, medium-, and high-dose groups was lower than that in the model group (P<0.05, P<0.01, respectively), and the expression of VEGF was inhibited: Nobitech stopped the low, medium, and high doses of VEGF All were lower than the model group (P<0.05, P<0.01 and P<0.01, respectively); inhibition of CAM angiogenesis: the number of CAM microvessels under the action of 2, 4 μg was significantly lower than that of the control group (P<0.01). Conclusion: Nifedipine can inhibit the growth and tumor angiogenesis in K562 nude mice. The mechanism may be related to the down-regulation of VEGF expression in tumor tissue.