Modulation of ghrelin axis influences the growth of colonic and prostatic cancer cells in vitro

Abstract

BackgroundThe risk of different cancers seems to be associated with obesity. Moreover, low ghrelin levels observed in obese people may be implicated in cancer development and progression. The aim of this study was to examine the direct effects of both forms of ghrelin (acylated and unacylated) and ghrelin receptor type 1a antagonist (D-Lys-GHRP-6) on the growth of murine colon cancer MC38 and human prostate cancer DU145 cell lines in vitro. MethodsThe cells were cultured for 72h in the presence of rat or human acylated ghrelin (rG, hG), human unacylated ghrelin (hUAG), D-Lys-GHRP-6 (GHS-RA) applied either alone or jointly. The cell line growth was assessed by the colorimetric Mosmann method. ResultshUAG (10−6, 10−7 and 10−10M) inhibited MC38 cancer cell growth and, at some concentrations (10−8, 10−9, 10−10M), enhanced the antineoplastic effect of GHS-RA (10−4M). In turn, GHS-RA evoked a biphasic effect on MC38 cancer growth: inhibitory at 10−4M and stimulatory at 10−5 and 10−6M. Moreover, GHS-RA at the highest examined concentration (10−4M) enhanced the cytostatic effect of FU. Human acylated and unacylated ghrelin and GHS-RA inhibited DU145 cancer growth with moderate and different potencies. A dose-response effect was observed for the inhibitory action of hG together with the synergistic effect of hUAG and GHS-RA. ConclusionThe obtained results indicate an involvement of the ghrelin axis in the growth regulation of colon and prostate cancers and may suggest new therapeutic options for these neoplasms.