黄精多糖对肝癌H_(22)移植瘤小鼠的抑瘤作用及机制研究

Anti-tumor Effects and Mechanism of Rhizoma Polygonati Polysaccharide on H_(22) Tumor Bearing Mice

目的研究黄精多糖对H22移植瘤小鼠的抑瘤作用,并探讨其作用机制。方法建立H22移植瘤小鼠模型。将模型小鼠随机分为5组:模型组,环磷酰胺组(20 mg·kg-1),黄精多糖高、中、低剂量组(400,200,100 mg·kg-1),连续灌胃给药10 d。测定瘤体质量,计算抑瘤率。新鲜瘤组织制备单细胞悬液,流式细胞术分析细胞周期分布,酶联免疫吸附法(ELISA)检测瘤组织中Caspase-3,8,9活性。结果黄精多糖各剂量组均能显著抑制肿瘤生长,高剂量组抑瘤率为54.5%,其作用接近环磷酰胺组(57.7%)。黄精多糖各剂量组能显著提高肿瘤组织中Caspase-3,8,9活性,与模型组比较差异有统计学意义(P<0.01)。黄精多糖中、高剂量组可显著增加G0/G1期细胞(P<0.05),减少G2/M期细胞(P<0.01),高剂量组还可减少S期细胞(P<0.05)。结论黄精多糖对肝癌H22移植瘤小鼠具有显著的抑瘤作用,其作用机制可能是通过影响细胞周期分布,将肿瘤细胞阻滞于G0/G1期,抑制细胞增殖,并通过激活Caspase系统诱导肿瘤细胞凋亡。

Polygonati Polysaccharide on H. Tumor Bearing Mice Department of Pharmacy, Nanyang Central Hospital, Nanyang Henan University of Traditional Chinese Medicine, Zhengzhou Abstract： Objective To investigate the anti-tumor effects of Rhizoma Polygonati polysaccharide （RPP） on Ha tumor bearing mice and to explore its mechanisms. Methods Ha tumor bearing mice model was established and the model mice were divided into 5 groups, model group, cyclophosphamide （CTX） group（20 mg.kg^-1）, and high-, middle- and low-dose（400, 200, 100 mg.kg^-1） RPP groups. After oral administration for successive 10 days, all mice were killed, and the tumor tissue was dissected and weighted. The tumor inhibition rate was calculated. The cell cycle was determined by flow cytometry, and the activity of Caspase-3, 8, 9 was detected by enzyme linked immunosorbent assay （ELISA）. Results All doses of RPP significantly inhibited the tumor growth, and the tumor inhibition rate in high-dose RPP was 54.5 %, close to 57.7 % in the CTX group. Moreover, RPP significantly enhanced the activity of easpase-3, 8, 9 in the tumor tissue （P 〈 0.01 compared with that in the model group）. The ratio of Go/G1 cells was significantly increased （P 〈 0.05）, and the ratio of G2/M cells was significantly reduced in middle- and high-dose RPP groups as compared with the control group（P 〈 0.01 ）. Furthermore, 400 mg.kg^-1 RPP also reduced the S phase cells count （P 〈 0.05）. Conclusion RPP has obvious anti-tumor effect on H22 tumor bearing mice. The mechanism may be related to regulating the cell cycle distribution, arresting the tumor cell in G0/G1 phase, inhibiting the cell proliferation and activating the caspase system to induce apoptosis.