Jacobs E, Watson S A, Ellis I O, Hardcastle J D, Robertson J F
Dept. of Surgery, City Hospital, Nottingham, U.K.
Eur J Cancer. 1997 Jun;33(7):1130-5. doi: 10.1016/s0959-8049(97)00070-1.
Onapristone is a progesterone antagonist which inhibits the growth of mammary tumours in mice. The effect of Onapristone and concomitant oestrogen (E2) supplements on the growth of five human gastrointestinal cancer xenografts was examined. E2 stimulated RD19 (gastric tumour) tumour growth in female mice and tumours grew less well when also treated with Onapristone (P < 0.05). Onapristone had no effect on male mice bearing RD19 tumours or mice of either sex bearing MKN45G (gastric) tumours. PAN-1 (pancreatic) tumours were significantly stimulated by E2 (by 64% of control, P = 0.02) and Onapristone treatment inhibited E2 stimulated growth (52% reduction of E2 control, P > 0.05). C146 (colorectal) tumour growth was not stimulated by E2 nor inhibited by Onapristone. E2 stimulated formation of AP5LV (colorectal) tumour nodules (in lungs) (mean 38-52, P = 0.001). Onapristone significantly reduced the number of nodules (mean 32, P < 0.05) only in female mice not given E2. Xenografts of some GI tumour cell lines grow at different rates in male and female mice. E2 may cause additional growth stimulation and E2 stimulated growth can be reversed by Onapristone to basal levels.
孕三烯酮是一种孕酮拮抗剂,可抑制小鼠乳腺肿瘤的生长。研究了孕三烯酮及同时补充雌激素(E2)对五种人胃肠道癌异种移植瘤生长的影响。E2刺激雌性小鼠的RD19(胃肿瘤)肿瘤生长,当同时用孕三烯酮治疗时肿瘤生长较差(P<0.05)。孕三烯酮对携带RD19肿瘤的雄性小鼠或携带MKN45G(胃)肿瘤的两性小鼠均无影响。E2显著刺激PAN-1(胰腺)肿瘤生长(为对照的64%,P=0.02),孕三烯酮治疗可抑制E2刺激的生长(比E2对照降低52%,P>0.05)。E2既不刺激C146(结肠直肠)肿瘤生长,孕三烯酮也不抑制其生长。E2刺激AP5LV(结肠直肠)肿瘤结节(在肺中)形成(平均38 - 52个,P = 0.001)。仅在未给予E2的雌性小鼠中,孕三烯酮显著减少了结节数量(平均32个,P<0.05)。一些胃肠道肿瘤细胞系的异种移植瘤在雄性和雌性小鼠中的生长速率不同。E2可能会导致额外的生长刺激,且E2刺激的生长可被孕三烯酮逆转至基础水平。