α-Chemokine growth factors for adenocarcinomas;: a synthetic peptide inhibitor for α-chemokines inhibits the growth of adenocarcinoma cell lines

Purpose: The experiments aimed to determine if alpha-chemokine inhibitors are effective suppressors of the growth of adenocarcinomas, a neoplasm with a high mortality rats, Methods: Expression of growth-related oncogene (GRO alpha) and interleukin-8 (IL-8) was determined by enzyme-linked immunosorbent assay. Inhibition alpha-chemokine binding to tumor cells was assessed in the presence and absence of the hexapeptide, antileukinate, 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays were performed to determine the effect of alpha-chemokines, monoclonal antibodies (mAb), and antileukinate on cell proliferation. Finally, antileukinate inhibition of human, lung adenocarcinoma tumor growth, was determined in BALB/c nude mice. Results: All of the adenocarcinomas tested produced either GRO alpha or IL-8 or both. Proliferation of lung, stomach and colon adenocarcinoma cells was inhibited by anti-GRO alpha mAb and/or anti-IL-8 mAb while recombinant human GRO alpha stimulated the proliferation of lung and stomach adenocarcinomas. Antileukinate inhibited GRO alpha binding to specific receptors on adenocarcinoma cells and inhibited the proliferation of all adenocarcinomas tested. Colon-derived adenocarcinomas specifically bound IL-8 and this binding was also inhibited by antileukinate. Administration of antileukinate in vivo inhibited the tumor growth of adenocarcinoma A549. Conclusions: GRO alpha and IL-8 are necessary for the growth of lung, stomach and colon adenocarcinomas, and can be inhibited by the hexapeptide, antileukinate. The findings suggest the possibility of using alpha-chemokine receptor inhibitors in the treatment of adenocarcinoma.