The effect of onapristone, a progesterone antagonist, on the growth of human gastrointestinal cancer xenografts.
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.
Jacobs
E
E
Dept. of Surgery, City Hospital, Nottingham, U.K.
Watson
S A
SA
Ellis
I O
IO
Hardcastle
J D
JD
Robertson
J F
JF
D000704:Analysis of Variance; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000737:chemistry / Q000188:drug therapy / Q000473:pathology; D004354:Drug Screening Assays, Antitumor; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000473:pathology; D006067:Gonanes / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D010190:Pancreatic Neoplasms / Q000737:chemistry / Q000188:drug therapy / Q000473:pathology; D011897:Random Allocation; D011980:Receptors, Progesterone / Q000032:analysis; D012737:Sex Factors; D013274:Stomach Neoplasms / Q000737:chemistry / Q000188:drug therapy / Q000473:pathology; D014183:Transplantation, Heterologous; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
D000970:Antineoplastic Agents; D004967:Estrogens; D006067:Gonanes; D011980:Receptors, Progesterone; C053238:onapristone