INHIBITORY EFFECTS OF GINSENOSIDE RH-2 ON TUMOR-GROWTH IN NUDE-MICE BEARING HUMAN OVARIAN-CANCER CELLS

Ginsenoside Rh-2 (Rh-2), isolated from an ethanol extract of the proce ssed root of Panax ginseng CA Meyer, inhibits the growth of B16 melano ma cells, This study was designed to evaluate the ability of Rh-2 to i nhibit growth of human ovarian cancer cells (HRA) in vitro and in nude mouse. Rh-2 inhibited proliferations of various established human ova rian 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 ce lls were inoculated s.c. into the right flank of nude mice, all mice f ormed 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 sign ificantly inhibited, compared to treatment with CDDP alone. When mice were treated p.o. with Rh-2 daily (but not meekly), the tumor growth w as significantly (P<0.01) inhibited, compared to CDDP treatment alone, When Rh-2 was combined with CDDP, the degree of tumor growth retardat ion 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 t he order of 1 mg/kg, 2 mg/kg and 4 mg/kg, whereas p.o. and daily admin istration of Rh-2 (0.4 to 1.6 mg/kg) not only had antitumor activity c omparable 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 res ult in ally adverse side-effects as confirmed by monitoring hematocrit values and body weight, unlike 4 mg/kg CDDP, which had severe side-ef fects. It is noteworthy that p.o. but not i.p. treatment with Rh-2 res ulted in induction of apoptotic cells in the tumor in addition to augm entation of the natural killer activity in spleen cells from tumor-bea ring nude mice. Thus, particularly in view of the toxicity of CDDP, Rh -2 alone would seem to warrant further evaluation for treatment of rec urrent or refractory ovarian tumor.