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

Abstract

Purpose: The experiments aimed to determine if α-chemokine inhibitors are effective suppressors of the growth of adenocarcinomas, a neoplasm with a high mortality rate. Methods: Expression of growth-related oncogene (GROα) and interleukin-8 (IL-8) was determined by enzyme-linked immunosorbent assay. Inhibition of α-chemokine binding to tumor cells was assessed in the presence and absence of the hexapeptide, antileukinate. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenylte-trazolium bromide assays were performed to determine the effect of α-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 GROα or IL-8 or both. Proliferation of lung, stomach and colon adenocarcinoma cells was inhibited by anti-GROα mAb and/or anti-IL-8 mAb while recombinant human GROα stimulated the proliferation of lung and stomach adenocarcinomas. Antileukinate inhibited GROα 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: GROα 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 α-chemokine receptor inhibitors in the treatment of adenocarcinoma.