Effect of tumour size on the in vivo growth inhibition of human colon carcinoma cells (HT-29) by colon mitosis inhibitor.
We have previously shown that the colon mitosis inhibitor (CMI) suppresses the growth of transplanted HT-29 human colon carcinoma cells by approximately 40%. However, this effect declined along the time-course, as the inoculums progressively grew larger. In the present work we designed a test to assess the effectiveness of CMI as a function of tumour size. After ranking the terminal tumours by ascending size in the control group and the CMI group the growth inhibition was calculated at each rank position. The observed negative correlation between control tumour size and CMI inhibition (r = -0.94, p < 0.001) clearly demonstrated decreased growth inhibition with increased tumour size. Consequently, a retrospective analysis of the smallest and slowest growing tumours showed a profound growth inhibition (72-81%, p < 0.008), whereas a similar analysis of the large and fast growing tumours revealed no significant CMI effect. The increased CMI effect among slow growing tumours was apparently not associated with increased susceptibility to CMI in a subset of slow growing cells because the slow growing subclone HT-29A4 did not show increased CMI effect. Furthermore, HT-29A4 displayed a similar tendency of decreased CMI effect with increased tumour size (r = -0.70, p < 0.001). Interestingly, the same tendency of increased growth inhibitory effect on smaller tumours was also seen with retinoic acid and difluoromethylornithine (r = -0.96, p < 0.001). The apparent enhanced responsiveness among small tumours underlines the importance of early chemoprevention and chemotherapy.
Paulsen
J E
JE
Department of Environmental Medicine, National Institute of Public Health, P.O. Box 4404, Nydalen, 0403 Oslo, Norway. jan.erik.paulsen@folkehelsa.no
Elgjo
K
K
D000230:Adenocarcinoma / Q000473:pathology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002455:Cell Division / Q000187:drug effects; D002999:Clone Cells / Q000187:drug effects / Q000637:transplantation; D003110:Colonic Neoplasms / Q000473:pathology*; D018450:Disease Progression; D000518:Eflornithine / Q000494:pharmacology / Q000627:therapeutic use; D006131:Growth Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009842:Oligopeptides / Q000494:pharmacology / Q000627:therapeutic use*; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives; D014212:Tretinoin / Q000494:pharmacology / Q000627:therapeutic use; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000637:transplantation; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D006131:Growth Inhibitors; D009842:Oligopeptides; D014212:Tretinoin; C023866:pyroglutamyl-histidyl-glycine; D011761:Pyrrolidonecarboxylic Acid; D000518:Eflornithine