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. 1991 Jan;117(1):37–42. doi: 10.1007/BF01613194

Influence of gastrin, gastrin receptor blockers, epidermal growth factor, and difluoromethylornithine on the growth and the activity of ornithine decarboxylase of colonic carcinoma cells

S Eggstein 1,✉, A Imdahl 1, M Kohler 2, M Waibel 1, E H Farthmann 1
PMCID: PMC12201485  PMID: 1997467

Abstract

Polyamines are essential factors of cell growth and differentiation. Modulation of the cellular polyamine content by 2-difluoromethylornithine (DFMO) inhibiting ornithine decarboxylase (ODC), or by hormones inducing ODC, influences cell growth. Gastrin acts trophically on some colonic carcinomas and their growth is inhibited by gastrin receptor blockers. The mechanism of the trophic action of gastrin on colonic carcinomas is not known. In this study the effect of gastrin, gastrin receptor blockers, epidermal growth factor (EGF) and DFMO on growth and ODC activity of four human colon carcinoma cell lines (SW 403, SW 1116, LS 174 T and Lovo) was investigated. Growth and ODC activity of all cell lines were inhibited by DFMO. Growth of the SW 403 cell line was increased by gastrin and inhibited by the gastrin receptor blocker benzotrypte. The other cell lines did not respond to gastrin and the gastrin receptor blocker. In SW 403 cells ODC activity was increased by gastrin, and was also elevated after treatment with the gastrin receptor blocker. These in vitro results were confirmed by studies on tumours that developed from SW 403 cells in nude mice. Combination of benzotrypte and DFMO did not enhance the antiproliferative effect. EGF increased growth of SW 403 cells, but no induction of ODC activity was measured. LS 174 T cells were not stimulated by EGF. Medium replacement was the strongest stimulus of ODC activity in SW 403 cells already inducing ODC after 3 h. During cell culture ODC activity was high after seeding and decreased continuously with increasing cell density. These data suggest that gastrin induces ODC in gastrin-sensitive colonic carcinoma cells. DFMO appears to be a valuable antiproliferative agent in colonic carcinoma cells.

Key words: Ornithine decarboxylase, 2-difluoromethyl-ornithine, Colonic carcinoma cell lines, Gastrin, Gastrin receptor blockers, EGF

Abbreviations

ODC

Ornithine decarboxylase

DFMO

2-difluoromethylornithine

EGF

epidermal growth factor

Footnotes

Supported by Deutsche Forschungsgemeinschaft (DFG)

References

  1. Bauknecht T, Schwall M, Peters H, Schwörer D, Wagner E, Pfleiderer A (1987) Expression of ornithine decarboxylase activity and putrescine, spermidine and spermine in specimens of gynecological tumors and their possible clinical relevance. Cancer J 1:318–325 [Google Scholar]
  2. Celano P, Baylin SB, Giardiello FM, Nelkin BD, Casero RA (1988) Effect of polyamine depletion on c-myc expression in human colon carcinoma cells. J Biol Chem 263:5491–5494 [PubMed] [Google Scholar]
  3. Eggstein S, Imdahl A (1988) Influence of pentagastrin and proglumide on human colorectal carcinoma. Chir Forum Exp Klin Forsch 366:21–24 [Google Scholar]
  4. Fitzpatrick LR, Wang P, Johnson LR (1987) Effect of epidermal growth factor on polyamine synthesizing enzymes in rat enterozytes. Am J Physiol 252:G209-G214 [DOI] [PubMed] [Google Scholar]
  5. Holm I, Perrson L, Stjernborg L, Thorsson L, Heby O (1989) Feedback control of ornithine decarboxylase expression by polyamines. Biochem J 258:343–350 [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Imdahl A, Eggstein S, Crone C, Farthmann EH (1989) Growth of colorectal carcinoma cells: regulation in vitro by gastrin, pentagastrin and the gastrin-receptor antagonist proglumide. J Cancer Res Clin Oncol 115:388–392 [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Johnson LR (1981) Regulation of gastrointestinal growth. In: Johnson LR (ed) Physiology of the gastrointestinal tract. Raven, New York, pp 169–196 [Google Scholar]
  8. Johnson LR, Tseng C-C, Tipnis UR, Haddox MK (1988) Gastric mucosal ornithine decarboxylase: localisation and stimulation by gastrin. Am J Physiol 255:G304-G312 [DOI] [PubMed] [Google Scholar]
  9. Kingsnorth AN, Lumsden AB, Wallace HM (1984) Polyamines in colorectal cancer. Br J Surg 71:791–794 [DOI] [PubMed] [Google Scholar]
  10. Lowry O, Rosebourgh L, Farr A, Randall R (1951) Protein measurement with the folin reagent. J Biol Chem 193:265–275 [PubMed] [Google Scholar]
  11. Lundell L, Rosengren E (1986) Polyamine levels in human gastric carcinoma. Scand J Gastroenterol 21:829–832 [DOI] [PubMed] [Google Scholar]
  12. Malt AR, Kingsnorth AN, Lamuraglia GM, Lacaine F, Ross JS (1985) Chemoprevention and chemotherapy by inhibition of ornithine decarboxylase activity and polyamine synthesis: colonic, pancreatic, mammary, and renal carcinomas. Adv Enzyme Regul 24:93–102 [DOI] [PubMed] [Google Scholar]
  13. Maudsley DV, Leif J, Kobayashi T (1976) Ornithine decarboxylase in rat small intestine: stimulation with food or insulin. Am J Physiol 231:1557–1561 [DOI] [PubMed] [Google Scholar]
  14. Parko WB, Kenny FT (1971) Hormonal stimulation of hepatic ornithine decarboxylase. Biochem Biophys Res Commun 43:346–350 [DOI] [PubMed] [Google Scholar]
  15. Pegg AE, McCann PP (1982) Polyamine metabolism and function. Am J Physiol 243:C212-C221 [DOI] [PubMed] [Google Scholar]
  16. Persson L, Oredsson SM, Anehus S, Heby O (1985) Ornithine decarboxylase inhibitors increase the cellular content of the enzyme: implications for translational regulation. Biochem Biophys Res Commun 131:239–245 [DOI] [PubMed] [Google Scholar]
  17. Persson L, Holm I, Heby O (1986) Translational regulation of ornithine decarboxylase by polyamines. FEBS Lett 205:175–178 [DOI] [PubMed] [Google Scholar]
  18. Rosewicz S, Lewis LD, Liddle AR, Logsdon CD (1988) Effects of cholecystokinin on pancreatic ornithine decarboxylase gene expression. Am J Physiol 255:G818-G821 [DOI] [PubMed] [Google Scholar]
  19. Seidel ER, Tabata K, Dembinski AB, Johnson LR (1985) Attenuation of trophic response to gastrin after inhibition of ornithine decarboxylase. Am J Physiol 249:G16-G20 [DOI] [PubMed] [Google Scholar]
  20. Seidel ER, Snyder RG (1989) Pentagastrin induction of spermine/spermidineN1-acetyltransferase and mucosal polyamines. Am J Physiol 256:G16-G21 [DOI] [PubMed] [Google Scholar]
  21. Tempero MA, Nishioka K, Knott K, Zettermann RK (1989) Chemoprevention of mouse colon tumors with difluoromethyl-ornithine during and after carcinogen treatment. Cancer Res 49:5793–5797 [PubMed] [Google Scholar]
  22. Tutton PJM, Barkla DH (1986) Comparison of the effects of an ornithine decarboxylase inhibitor on the intestinal epithelium and on intestinal tumors. Cancer Res 46:6091–6094 [PubMed] [Google Scholar]
  23. Upp JR, Townsend CM, Thompson JC (1987) Tumor polyamine levels predict therapeutic response to α-difluoromethylornithine in human colon cancers in nude mice. Surg Forum 38:421–423 [Google Scholar]
  24. Upp JR, Saydjari R, Townsend CM, Singh P, Barranco SC, Thompson JC (1988) Polyamine levels and gastrin receptors in colon cancers. Ann Surg 207:662–669 [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Zhang S-Z, Luk GD, Hamilton SR (1988) α-Difluoromethylorni-thine-induced inhibition of growth of autochthonous experimental colonic tumors produced by azoxymethane in male F344 rats. Cancer Res 48:6498–6503 [PubMed] [Google Scholar]

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