Mycophenolate Mofetil Alone and in Combination with Tacrolimus Inhibits the Proliferation of HT-29 Human Colonic Adenocarcinoma Cell Line and Might Interfere with Colonic Tumorigenesis

• Published in: Anticancer research 2018-06, Vol.38 (6), p.3333-3339
• Main Authors: Ling, Galina, Lamprecht, Sergio, Shubinsky, George, Osyntsov, Lidia, Yerushalmi, Baruch, Pinsk, Ilya, Pinsk, Vered, Ling, Eduard
• Format: Article
• Language: English
• Subjects: Adenocarcinoma; Adenocarcinoma - drug therapy; Adenocarcinoma - metabolism; Adenocarcinoma - pathology; Adenomatous Polyposis Coli - drug therapy; Adenomatous Polyposis Coli - metabolism; Adenomatous Polyposis Coli - pathology; Antibiotics, Antineoplastic - administration & dosage; Antibiotics, Antineoplastic - pharmacology; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Carcinogenesis - drug effects; Cell cycle; Cell Cycle Checkpoints - drug effects; Cell proliferation; Cell Proliferation - drug effects; Colon - drug effects; Colon - pathology; Colonic Neoplasms - drug therapy; Colonic Neoplasms - metabolism; Colonic Neoplasms - pathology; Colorectal cancer; Drug Synergism; Familial adenomatous polyposis; Flow cytometry; HT29 Cells; Humans; Immunosuppressive Agents - administration & dosage; Immunosuppressive Agents - pharmacology; Ki-67 Antigen - metabolism; Kidney transplantation; Mycophenolate mofetil; Mycophenolic acid; Mycophenolic Acid - administration & dosage; Mycophenolic Acid - pharmacology; Patients; Polyps; Tacrolimus; Tacrolimus - administration & dosage; Tacrolimus - pharmacology; Transplantation; Tumorigenesis
• ISSN: 0250-7005; 1791-7530
• DOI: 10.21873/anticanres.12599

Familial adenomatous polyposis (FAP) was found to be completely reversed in a patient treated with mycophenolate mofetil (MMF) and tacrolimus following kidney transplantation. In this preliminary study, we assessed whether MMF and tacrolimus alone or in combination interfere with the cell cycle and proliferation in a human colonic adenocarcinoma cell line and in the colonic polyps of the patient with FAP. Human colonic adenocarcinoma HT-29 cells were treated with tacrolimus and MMF alone and in combination at different concentrations. Cell viability and proliferation were assessed using the MTT assay. Cell-cycle distribution was analyzed by flow cytometry. Expression of Ki-67, a marker of mitotic activity, was evaluated in the patient's colonic polyps before and under drug treatment. MMF in combination with tacrolimus induced S-phase cell-cycle arrest and markedly inhibited HT-29 cell proliferation. Ki-67 expression in the patient's colonic polyps was significantly reduced following combined tacrolimus and MMF treatment. MMF and tacrolimus synergistically inhibited proliferation of a human colonic adenocarcinoma cell line and interfered with the expansion of colonic crypt proliferation in the polyp from a patient with FAP. The results confirm our clinical observation and indicate the possibility of novel approach to therapy of colorectal neoplasia.