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SMS 201.995 Inhibits in Vitro and in Vivo Growth of Human Colon Cancer¹

Department of Surgery, University of New South Wales, The St. George Hospital, Kogarah, 2217, Sydney, New South Wales [D. Y. D., D. L. M.], and Ludwig Institute for Cancer Research, Royal Melbourne Hospital, Melbourne, 3000 Victoria [R. H. W.], Australia

The effect of a long-acting somatostatin analogue SMS 201.995 (SMS; Sandoz) on basal and gastrin-stimulated growth of 4 human colon cancer lines was studied in vitro and in vivo. Proliferation assay was done with overnight [⁷⁵Se]selenomethionine uptake after 5 days of incubation. Gastrin concentrations used were 5e-10 M and 1e-7 M. SMS concentrations were from 2e-12 M to 2e-7 M. Cell lines LIM 1215, LIM 2405, and LIM 2412 were inhibited dose-dependently in both basal and gastrin-stimulated groups. LIM 1863 was slightly stimulated. Based on in vivo growth characteristics, LIM 2412 and LIM 2405 were selected for xenograft study. The dose of 50 µg/kg/day was arrived at after a preliminary experiment showed it to be safe and effective. The LIM 2412 xenografts in the SMS-treated animals were 473.3 ± 99.9 (SD) versus 838.1 ± 111.3 mm³ in control (P < 0.05) after 20 days. The LIM 2405 tumors were also significantly inhibited (81.2 ± 30.0 versus 245.7 ± 48.3 mm³, P < 0.01). The effect of SMS appeared to be reversible. Oral SMS at 200 µg/kg/day was not absorbed. This study suggests that SMS may have direct antitumor effects in human colon cancer.

¹ D. Y. D. is an Equity and Merit Scholarship Scheme Merit Scholar sponsored by the Australian International Development Assistance Bureau. The generous support of the R. T. Hall Trust and the Clive and Vera Ramaciotti Foundations for our laboratory is greatly appreciated.

² To whom requests for reprints should be addressed.

Received 6/ 4/91. Accepted 11/21/91.

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