目的 探讨扶正抑瘤汤对裸鼠卵巢癌移植瘤的抑制作用并探讨及作用机制。方法 40只裸鼠接种人卵巢癌细胞A2780,复制荷瘤模型后,随机分为4组,每组10只:分别为对照组和扶正抑瘤汤大、中、小剂量组;分别给予生理盐水、和不同剂量扶正抑瘤汤(30 g/kg 、20 g/kg、10 g/kg)灌胃,连续3W。停药第2天测量各组裸鼠肿瘤体积后,处死裸鼠,剥离肿瘤称重。流式细胞仪检测肿瘤组织的细胞周期、Western Blot法检测肿瘤组织的PCNA和VEGF蛋白表达、ELISA法检测裸鼠外周血IL-2和INF-γ水平。结果 与对照组相比,各剂量组裸鼠的肿瘤体积和重量均明显降低(P<0.05);随着扶正抑瘤汤剂量的增大,抑制肿瘤生长的作用更明显(P<0.01)。随着药物剂量加大,肿瘤组织G1期细胞随之增多,而S期+G2细胞则随之减少 (P<0.01)。扶正抑瘤汤可明显下调肿瘤组织的PCNA和VEGF蛋白表达、上调外周血IL-2和INF-γ的水平,其作用呈剂量依赖性(P<0.01)。结论 扶正抑瘤汤能抑制卵巢癌荷瘤鼠瘤组织的生长,作用呈剂量依赖性;作用机制可能与扶正抑瘤汤对瘤组织细胞周期的调控、下调瘤组织PCNA、VEGF表达以及提高免疫功能等途径有关。
Abstract
Objective To explore the inhibitive effects of Fuzheng-yiliu Decoction on ovarian cancer and its mechanism. Methods The tumor bearing models of human ovarian cancer were established in 40 nude mice, which were randomly divided into 4 groups: the control group, the large dosage group, the moderate dosage group and the small dosage group, and respectively received saline or Fuzheng-yiliu with different concentrations (30g/kg,20g/kg or10g/kg) by gavage administration for 3 weeks. After the tumor sizes were measured, the mice in each group were sacrificed with the tumor peeled and weighed. Cell cycles in the tumor tissue were determined by flow cytometry. The expression levels of PCNA and VEGF protein in the tumor tissue were determined by Western blotting. ELISA was used to determine the serum levels of IL-2 and INF-γ. Results When compared to the control group, the tumor sizes and weight were all significantly decreased in the Fuzheng-yiliu Decoction groups(P<0.05), and the inhibitive effect was more intensive with the dosage increased(P<0.01). More cells at G1 stage with fewer cells at S stage and G2 stage were detected in the tumor tissue with the dosage increased(P<0.01).The protein expression of PCNA and VEGF in the tumor tissue were significantly down-regulated, while the serum levels of IL-2 and INF-γ were significantly up-regulated by Fuzheng-yiliu Decoction in a dosage-dependent model(P<0.01). Conclusion Fuzheng-yiliu Decoction can inhibit the growth of transplanted ovarian cancer in nude mice in a dosage-dependent model; the possible mechanism may lie in the cell-cycle regulation,the falling-regulation of PCNA and VEGF expression in tumor tissue,and the improvement of immune function.
关键词
扶正抑瘤汤 /
卵巢癌 /
抑制作用 /
作用机制 /
动物实验 /
实验研究
Key words
Fuzheng-yiliu Decoction /
Ovarian cancer /
Inhibitive effect /
Animal experiment /
Experimental study
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基金
国家自然科学基金青年创新基金(81402156)
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