Leptin promotes the growth of Colon 38 cancer cells and interferes with the cytotoxic effect of fluorouracil in vitro

Abstract

Introduction: Epidemiological studies underline the fact that obesity represents a significant risk factor for the development of several cancers, one of which is cancer of the colon. Moreover, multiple recent data indicate that some adipose tissue-derived hormones may influence the growth of malignant cells. Leptin, the product of the ob gene, is one of these. However, the evidence from research is still contradictory regarding the role of leptin in colon cancer. The aim of our study was to examine the direct effect of leptin at various concentrations (from 10^-5 to 10^-12 M) when applied alone or jointly with fluorouracil (the classical cytotoxic drug for colon cancer) at two concentrations (0.25 mg/ml and 2.5 mg/ml) on the growth of murine Colon 38 cancer cells in vitro.
Colon 38 cancer cells were preincubated in RPMI 1640 medium supplemented with foetal calf serum for 24 hours. The cells were then cultured for a further 72 hours in the presence of various concentrations of the substances under examination, applied either alone or jointly. The growth of the Colon 38 cell line was assessed by a colorimetric kit based on the modified Mosmann method.
Results: We found that leptin increased the growth of murine Colon 38 cancer at concentrations of 10^-6, 10^-7 M and 10^-10, 10^-11, 10^-12 M. Its stimulatory effect was fairly slight, with an increase in cancer growth of 5% to 15% as compared to controls. As we expected, fluorouracil at both the concentrations examined inhibited the growth of Colon 38 cancer maximally up to 28% (2.5 mg/ml) and 34% (0.25 mg/ml) of controls, with a stronger effect obtained from higher doses. Leptin did not modulate the cytotoxic effect of fluorouracil applied at the higher concentration (2.5 mg/ml) but, unexpectedly, at concentrations of 1^-9 and 10^-10 M it heightened the cytotoxic effect of fluorouracil given at a lower concentration (0.25 mg/ml).
Conclusions: These data indicate that leptin is involved in the regulation of colon cancer growth and it may even heighten the cytotoxic effect of fluorouracil.