ヌードマウスを用いた非ホルモン性抗癌剤による前立腺癌化学療法に関する研究

Abstract

The interest of many urologists in chemotherapy of carcinoma of the prostate has recently arisen in treatment of intractable cases to anti-androgen therapy. Several clinical trials in broadly organized project teams, such as NPCP in U.S.A., are now progressing, but they have not produced definitive conclusions yet. We herein report the experimental results on effectiveness of several non-hormonal anti-tumor agents tested in nude mice with tumors resulting from inocculation of cultured EB 33 cells which had been established from human prostatic cancer tissue. Three representative chemotherapeutics such as 5-fluorouracil (5-FU) or Futraful, a masked compound of 5-FU, cyclophosphamide (CPM) and vincristine (VCR) were principal candidates for the experiment, and cis-diamminedichloride platinum (CDDP) and Estracyt were also tested. The effect of these drugs was evaluated through statistical analysis of the tumor growth curve compared to that of the control group. The drugs were usually injected intraperitoneally for consecutive 14 days except for VCR, 7 times per 3 days, and CDDP, for consecutive 5 days. The results obtained are as follows. 1) 5-FU, 20 mg/kg, did not show tumor reduction, while 60 mg/kg ofFT did a tendency of growth inhibition compared to controls with less decrease of body weight than 5-FU. 2) CPM and VCR brought a significant tumor reduction compared to controls at the doses of 10 mg and 0.45 mg per kg, respectively. In VCR group, however, 3 of6 animals suffered from distension of intestine during experimental period, while only minimal loss of body weight occurred in CPM group. 3) A combination of 2 of 3, and all of the 3 above mentioned agents were also examined if there was a synergic effect among them. CPM plus VCR showed an additive effect, but neither multiplied nor additive effect was recognized in other combinations. 4) Estracyt, 20 mg/kg, did not show any significant change m tumor growth, although rather marked decrease of body weight occurred at this dose. 5) CDDP showed apparent inhibition of tumor growth, although shortage of numbers of tested animals prevented from statistical analysis. It is concluded through the experimental result that CPM and/or VCR, and CDDP seem to be effective chemotherapeutics for carcinoma of the prostate. The result has almost corresponded to those in clinical reports up to date. This experimental model will be a useful tool in further study for carcinoma of the prostate, since EB 33 cells well preserve original characteristics as human prostatic epithelial cells.