葫芦素片对移植性宫颈癌荷瘤小鼠的肿瘤作用机制研究

Effect of Cucurbitacin Tablets on Transplanted Cervical Cancer-bearing Mice and Its Mechanism

目的:探讨葫芦素片对移植性宫颈癌荷瘤小鼠的肿瘤作用机制。方法 :将40只Balb/c小鼠进行移植性宫颈癌荷瘤模型造模,随机分为模型组、阳性药组、小剂量组及大剂量组,每组10只,并对小剂量组及大剂量组小鼠灌胃葫芦素片,比较各组小鼠肿瘤体积及重量,计算肿瘤生长抑制率。将小鼠肿瘤分为两份,一份采用伊红-美兰(HE)染色进行病理组织学观察,另一部分采用荧光免疫组化法。观察血管内皮生长因子(VEGF)、血管内皮生长因子受体-2(VEGFR-2)及低氧诱导因子-1α(HIF-1α)的表达情况,并比较其相对表达量。结果:与模型组比较,大剂量组与小剂量组小鼠肿瘤组织体积与重量均显著降低(P<0.05);与阳性药组比较,大剂量组及小剂量组小鼠肿瘤生长抑制率较低(P<0.05)。病理观察结果显示,大剂量组与小剂量组小鼠肿瘤组织中均可见不同程度的癌细胞坏死及凋亡。免疫荧光染色结果显示,与模型组比较,大剂量组与小剂量组VEGF、VEGFR-2及HIF-1α蛋白的阳性表达均显著降低,且相对表达量亦显著降低(P<0.05)。结论 :葫芦素片对移植性宫颈癌荷瘤小鼠肿瘤具有较强的抑制活性,主要作用机制可能为抗血管生成作用。

Objective:To study the tumor inhibitory effect of cucurbitacin Tablets on transplanted cervical cancer cancer-bearing mice and its mechanism. Methods:Total 40 Balb/c transplanted cervical cancer cancer-bearing mice were divided into the model group,positive drug group,high dose group and low dose group,10 mice in each group. Cucurbitacin Tablets were given to the high dose group and low dose group,comparing the volume and weight of the tumors in each group and calculating the tumor growth inhibition rates. After the observation,the tumor tissues were divided into two parts. One part was treated with Yihong-Meilan(HE) for histopathological observation and the other with fluorescent immunohistochemistry. The expressions of vascular endothelial growth factor(VEGF),vascular endothelial growth factor receptor-2(VEGFR-2) and hypoxia-inducible factor-1α(HIF-1α) were observed and their relative expression levels were compared. Results:Compared with the model group,the tumor volume and weight were significantly reduced in the high dose group and low dose group(P< 0.05). Compared with the positive drug group,the tumor growth inhibition rate was reduced in the high-dose group and low-dose group. Pathological observations showed that in the high and low dose group,the tumor cells were significantly necrosis and apoptosis. Immunofluorescent staining shown,the expressions of VEGF,VEGFR-2 and HIF-1α and their relative expression levels were significantly reduced in the high and low dose group compared to the model group(P< 0.05). Conclusion:Cucurbitacin Tablets has strong inhibitory activity on tumors of transplanted cervical cancer-bearing mice,and its main mechanism may be anti-angiogenic effect.