E phage gene transfection associated to chemotherapeutic agents increases apoptosis in lung and colon cancer cells

Abstract

The limited ability of conventionaltherapies to achieve the long-termsurvival of metastatic lung and coloncancer patients suggests the need fornew treatment options. In this respect,genes encoding cytotoxic proteins havebeen proposed as a new strategy toenhance the antiproliferative activity ofdrugs, and combined therapies involvingsuch genes and classical antitumoraldrugs have been studied intensively. TheE gene from phiX174 encodes a membraneprotein with a toxic domain thatleads to a decrease in tumor cell growthrates. Therefore, in order to improve theanti-tumor effects of currently used chemotherapeuticdrugs on cancer cells, weinvestigated the association of the E suicidegene with these antineoplastic drugs.The E gene has antitumoral effects in bothlung and colon cancer cells. In addition,expression of this gene induces ultrastructuralchanges in lung cancer transfectedcells (A-549), although the significanceof these changes remains unknown. Theeffect of combined therapy (gene andcytotoxic therapy) enhances the inhibitionof tumor cell proliferation in comparisonto single treatments. Indeed, ourin vitro results indicate that an experimentaltherapeutic strategy based on thiscombination of E gene therapy and cytotoxicdrugs may result in a new treatmentstrategy for patients with advanced lungand colon cancer. © 2011 Landes Bioscience.