Inhibitory effects of ginsenoside Rh2 on tumor growth in nude mice bearing human ovarian cancer cells

Ginsenoside Rh-2 (Rh-2), isolated from an ethanol extract of the processed root of Panax ginseng CA Meyer, inhibits the growth of B16 melanoma cells, This study was designed to evaluate the ability of Rh-2 to inhibit growth of human ovarian cancer cells (HRA) in vitro and in nude mouse. Rh-2 inhibited proliferations of various established human ovarian cancer cell lines in a dose-dependent manner between 10 and 60 mu M in vitro and induced apoptosis at around the IC50 dose, When HRA cells were inoculated s.c. into the right flank of nude mice, all mice formed a palpable tumor within 14 days, Although i.p. administration of Rh-2 alone hardly inhibited the tumor growth, when Rh-2 was combined with cis-diamminedichloroplatinum(II) (CDDP) the tumor growth was significantly inhibited, compared to treatment with CDDP alone. When mice were treated p.o. with Rh-2 daily (but not meekly), the tumor growth was significantly (P<0.01) inhibited, compared to CDDP treatment alone, When Rh-2 was combined with CDDP, the degree of tumor growth retardation was not potentiated. The survival time was significantly (P<0.05) longer than that of medium alone-treated controls or the group treated with CDDP alone, Then, we examined whether p.o. administration of Rh-2 has a dose-dependent inhibitory effect on the tumor growth, I.p. and weekly administration of CDDP had more potent antitumor activity in the order of 1 mg/kg, 2 mg/kg and 4 mg/kg, whereas p.o. and daily administration of Rh-2 (0.4 to 1.6 mg/kg) not only had antitumor activity comparable to that of 4 mg/kg CDDP, but also resulted in a significant increase of the survival. Doses of Rh-2 used in this study did not result in ally adverse side-effects as confirmed by monitoring hematocrit values and body weight, unlike 4 mg/kg CDDP, which had severe side-effects. It is noteworthy that p.o. but not i.p. treatment with Rh-2 resulted in induction of apoptotic cells in the tumor in addition to augmentation of the natural killer activity in spleen cells from tumor-bearing nude mice. Thus, particularly in view of the toxicity of CDDP, Rh-2 alone would seem to warrant further evaluation for treatment of recurrent or refractory ovarian tumor.