HAMPT, A Novel Quadruple Drug Combination Designed for Cancer Metastatic Chemoprevention: From Hypothesis to Proof-of-concept

Abstract

Background:Highly Active Metastasis Preventing Therapy (HAMPT) is a quardruple drug combination consisting of mifepristone, aspirin, lysine and doxycycline.Objective:Based on our previous study, here, we further proved that HAMPT could effectively and safely prevent colon cancer metastasis.Methods:It was specifically designed for synergistically controlling key cancer metastatic pathways. The dose of HAMPT was designed at lower than the pharmaceutically-recommended dose, and thus the sub-healthy cancer survivors may take HAMPT safely and for a long time for metastasis chemoprevention.Results:HAMPT within its effective concentration range (1-50 µg/mL) showed no cytotoxicity to colon cancer cells HT-29 and CT-26, but significantly inhibited adhesion and invasion of these colon cancer cell lines to human umbilical vascular endothelial cells (HUVECs), and to Matrigel. HAMPT exhibits a good adhesion inhibited ratio, suggesting that it functions primarily by inhibiting adhesion of the cancer cells to HUVECs, rather than killing the cancer cells. At low concentrations, HAMPT also inhibited cancer cell migration. Flow cytometry analysis revealed that HAMPT had no significant effect on cell cycle, but inhibited IL-1β-induced expression of both E-selectin of HUVECs and Sialyl-Lewis X of HT-29. The in vivo experiment showed that HAMPT suppressed metastasis of CT-26 cells to mouse lungs in a dose-dependent manner. In the mouse model, HAMPT showed advantages in preventing metastasis over other combinations.Conclusion:The present study demonstrated that HAMPT is a novel quadruple drug combination that can safely and effectively prevent cancer metastasis.