Epidemiological studies underline that obesity represents a significant risk factor for development of several cancer among them colon cancer. Moreover, multiple recent data indicate that some of adipose tissue-derived hormones may influence the growth of malignant cells. Leptin, the product of the ob gene, is one of them. However, 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) applied alone or jointly with fluorouracil (the classical cytotoxic drug for colon cancer) at two concentrations (0.25 μg/ml and 2.5 μg/ml) on the growth of murine Colon 38 cancer cells in vitro.
Colon 38 cancer cells were preincubated in RPMI 1640 medium supplemented with fetal calf serum for 24 hours. Then the cells were cultured for 72 hours in the presence of various concentrations of the examined substances applied either alone or jointly. The growth of Colon 38 cell line was assessed by the colorimetric Mosmann method.
We have found that leptin increased the growth of murine Colon 38 cancer at the concentrations of 10−6, 10−7 M and 10−10, 10−11, 10−12 M. Its stimulatory effect was rather slight with enhancement of cancer growth by 8% to 15% as compared to controls. Fluorouracil, at both concentrations (0.25 μg/ml and 2.5 μg/ml) inhibited the growth of Colon 38 cancer up to 28% and 40% of controls, respectively. Leptin did not modulate the cytotoxic effect of fluorouracil applied at higher concentration (2.5 μg/ml) but unexpectedly it enhanced at the concentrations of 10−9 and 10−10 M the cytotoxic effect of fluorouracil given at lower concentration (0.25 μg/ml).
These data indicate that leptin is involved in the regulation of colon cancer growth and it may even enhance the cytotoxic effect of fluorouracil.
Grant No. 502-11-295 from the Medical University of Lodz.