Nakata H, Kikuchi Y, Tode T, Hirata J, Kita T, Ishii K, Kudoh K, Nagata I, Shinomiya N
Department of Obstetrics and Gynecology, National Defense Medical College, Tokorozawa, Saitama.
Jpn J Cancer Res. 1998 Jul;89(7):733-40. doi: 10.1111/j.1349-7006.1998.tb03278.x.
Ginsenoside Rh2 (Rh2), 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 Rh2 to inhibit growth of human ovarian cancer cells (HRA) in vitro and in nude mouse. Rh2 inhibited proliferations of various established human ovarian cancer cell lines in a dose-dependent manner between 10 and 60 microM 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 Rh2 alone hardly inhibited the tumor growth, when Rh2 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 Rh2 daily (but not weekly), the tumor growth was significantly (P<0.01) inhibited, compared to CDDP treatment alone. When Rh2 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 Rh2 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, (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 Rh2 used in this study did not result in any 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 Rh2 resulted in induction of apoptotic cells in the tumor in addition to augmentation of the natural killer activity in spleen cells from tumor-hearing nude mice. Thus, particularly in view of the toxicity of CDDP, Rh2 alone would seem to warrant further evaluation for treatment of recurrent or refractory ovarian tumor.
人参皂苷Rh2（Rh2）是从人参（Panax ginseng CA Meyer）加工根的乙醇提取物中分离得到的，它能抑制B16黑色素瘤细胞的生长。本研究旨在评估Rh2在体外和裸鼠体内抑制人卵巢癌细胞（HRA）生长的能力。Rh2在体外10至60微摩尔浓度范围内以剂量依赖方式抑制多种已建立的人卵巢癌细胞系的增殖，并在IC50剂量左右诱导细胞凋亡。将HRA细胞皮下接种到裸鼠右腹侧后，所有小鼠在14天内均形成可触及的肿瘤。虽然单独腹腔注射Rh2几乎不能抑制肿瘤生长，但当Rh2与顺二氯二氨铂（II）（CDDP）联合使用时，与单独使用CDDP治疗相比，肿瘤生长受到显著抑制。当小鼠每天（而非每周）口服Rh2时，与单独使用CDDP治疗相比，肿瘤生长受到显著（P<0.01）抑制。当Rh2与CDDP联合使用时，肿瘤生长延缓程度并未增强。其生存时间显著（P<0.05）长于单独用培养基处理的对照组或单独用CDDP处理的组。然后，我们研究了口服Rh2是否对肿瘤生长有剂量依赖性抑制作用。腹腔注射和每周一次注射CDDP时，按1毫克/千克、2毫克/千克和4毫克/千克的顺序具有更强的抗肿瘤活性，而口服且每日注射Rh2（0.4至1.6毫克/千克）不仅具有与4毫克/千克CDDP相当的抗肿瘤活性，还能显著延长生存期。与具有严重副作用的4毫克/千克CDDP不同，通过监测血细胞比容值和体重证实，本研究中使用的Rh2剂量未导致任何不良副作用。值得注意的是，口服而非腹腔注射Rh2除了增强荷瘤裸鼠脾细胞的自然杀伤活性外，还能诱导肿瘤中的凋亡细胞。因此，特别是考虑到CDDP的毒性，Rh2单独用于治疗复发性或难治性卵巢肿瘤似乎值得进一步评估。
