Wang Zhenhua, Zheng Qiusheng, Liu Ke, Li Gang, Zheng Rongliang
School of Life Sciences, Lanzhou University, Lanzhou, People's Republic of China.
Basic Clin Pharmacol Toxicol. 2006 Apr;98(4):411-5. doi: 10.1111/j.1742-7843.2006.pto_348.x.
Ginsenoside Rh(2), a panaxadiol saponins, possesses various antitumour properties. Cyclophosphamide, an alkylating agent, has been shown to possess various genotoxic and carcinogenic effects, however, it is still used extensively as an antitumour agent and immunosuppressant in the clinic. Previous reports reveal that cyclophosphamide is involved in some secondary neoplasms. In this study, the antitumour activity and genotoxic effect of oral intake of ginsenoside Rh(2) combined with intraperitoneal injection of cyclophosphamide was investigated. Meanwhile, C57BL/6 mice bearing B16 melanoma and Lewis lung carcinoma cells were respectively used to estimate the antitumour activity in vivo. The clastogenic activity in bone marrow polychromatic erythrocytes was assayed by frequency of micronucleus. The DNA damage in peripheral white blood cells was assayed by single cell gel electrophoresis as well. The results indicated that oral administration of Rh(2) (5, 10 and 20 mg/kg body weight) alone has no obvious antitumour activity and genotoxic effect in mice, while Rh(2) synergistically enhanced the antitumour activity of cyclophosphamide (40 mg/kg body weight) in a dose-dependent manner. Rh(2) decreased the micronucleus formation in polychromatic erythrocytes and DNA strand breaks in white blood cells in a dose-dependent way. Our results suggest that ginsenoside Rh(2) is able to enhance the antitumour activity and decrease the genotoxic effect of cyclophosphamide.
人参皂苷Rh(2)是一种人参二醇皂苷,具有多种抗肿瘤特性。环磷酰胺是一种烷化剂,已被证明具有多种遗传毒性和致癌作用,然而,它在临床上仍被广泛用作抗肿瘤药物和免疫抑制剂。先前的报道显示环磷酰胺与一些继发性肿瘤有关。在本研究中,研究了口服人参皂苷Rh(2)联合腹腔注射环磷酰胺的抗肿瘤活性和遗传毒性作用。同时,分别使用携带B16黑色素瘤和Lewis肺癌细胞的C57BL/6小鼠来评估体内抗肿瘤活性。通过微核频率测定骨髓多染红细胞中的致断裂活性。外周血白细胞中的DNA损伤也通过单细胞凝胶电泳进行测定。结果表明,单独口服Rh(2)(5、10和20mg/kg体重)对小鼠没有明显的抗肿瘤活性和遗传毒性作用,而Rh(2)以剂量依赖的方式协同增强了环磷酰胺(40mg/kg体重)的抗肿瘤活性。Rh(2)以剂量依赖的方式减少了多染红细胞中的微核形成和白细胞中的DNA链断裂。我们的结果表明,人参皂苷Rh(2)能够增强环磷酰胺的抗肿瘤活性并降低其遗传毒性作用。