人参皂甙Rg3联合三氧化二砷对人肝癌裸鼠MVD和PCNA的影响

Effect of Ginsenoside Rg3 Combined with Arsennic Trioxide on Tumor MVD and PCNA in Human Hepatic Carcinoma in Nude Mice

目的探讨人参皂甙Rg3联合三氧化二砷对肝癌裸鼠移植瘤模型的治疗作用,观察其对人肝癌裸鼠MVD和PCNA的影响。方法采用人肝癌细胞株Bel-7402细胞株,种植于32只雄性裸鼠皮下,随机均分成4组:联合用药组、Rg3组(5μg/g、10μg/g、20μg/g)、三氧化二砷组及对照组。实验自肿瘤接种第3天开始,人参皂甙Rg3,隔日灌胃,共20次;三氧化二砷每天40 ng/g,腹腔内注射,连续28 d。对照组用生理盐水。停药1周后,脱颈处死,完整取出瘤块,采用免疫组织化学法检测联合用药组、Rg3组、三氧化二砷组及对照组中细胞核增殖性抗原(PCNA),血管第Ⅷ因子在裸鼠肝癌移植瘤组织中的表达情况,并计数微血管密度(MVD)。结果Rg3组抑制新生血管形成作用强于三氧化二砷组,三氧化二砷组抑制肝癌细胞增殖作用强于Rg3组,人参皂甙Rg3与三氧化二砷联合用药,作用最强,可以明显抑制移植瘤肝癌细胞增殖。结论Rg3抑制肿瘤生长可能主要是通过抑制肿瘤血管生成来实现的,三氧化二砷对裸鼠肝癌移植瘤生长的抑制作用可能是通过抑制PCNA蛋白的表达。人参皂甙Rg3与三氧化二砷联合用药,对移植瘤肝癌细胞增殖性的抑制有协同作用。

Objective To study the effect of reducing the intratumoral microvessel density（MVD）and PCNA by ginsenoside Rg3 （Rg3） combined with Arsennic trioxide （As2O3）in transplanted human hepatic carcinoma in nude mice. Methods 32 male nude mice were randomly divided into 8 groups to receive Rg3 （5 μg/g,10 μg/g,20 μg/g） combined with arsennie trioxide （As2O3）,Rg3 （5 μg/g,10 μg/g,20 μg/ g） alone, arsennie trioxide（As2O3） （40 ng/g） alone and saline（0.5 mL, qd） respectively. 3 days after inoculated in nude mice, Rg3 was given by gastrogavage once every 2 days for 20 times in all, As2O3 was injected introperitoneally once a day for 28 days,a week after treatment being stopped,mice were killed, the intratumor MVD and PCNA were examined by immunohistoehemieal staining. Results The MVD value of Rg3 group was significantly lower than that of As2O3 group and control group,and the PCNA value of As2O3 group was significantly lower than that of Rg3 group and control group, the effect of inhibiting the proliferation of hepatoma cells treated by Rg3 combined with As2O3 was strongest. Conclusion Rg3 can obviously inhibit the growth of transplanted human hepatic carcinoma in nude mice through inhibiting aniogensis of malignant tumor. As2O3 may inhibit the growth of transplanted human hepatic carcinoma in nude mice mainly through laying down the expression of PCNA. Rg3 combined with As2O3 can significantly inhibit the proliferation of hepatoma cells,which proves to be synergistic action in treating hepatic carcinoma.