Open AccessAnti-tumor activity of gene transfer of the membrane-stable CD40L mutant into lung cancer cells
Author(s) -
Wei Xu,
Yan Li,
Xueli Wang,
Cuiyu Wang,
Weihong Zhao,
Jianzhong Wu
Publication year - 2010
Publication title -
international journal of oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.405
H-Index - 122
ISSN - 1019-6439
DOI - 10.3892/ijo_00000744
Subject(s) - cd40 , transfection , biology , cancer research , a549 cell , mutant , oncogene , cell culture , cell , adenocarcinoma , cancer , cd154 , cell cycle , lung cancer , genetic enhancement , microbiology and biotechnology , apoptosis , gene , in vitro , cytotoxic t cell , pathology , biochemistry , medicine , genetics
Gene transfer of CD40 ligand (CD40L) holds promise as a novel therapy for lymphoid malignancies and a number of solid carcinomas because of its multiple anti-tumor activities. However, membrane-bound CD40L can be cleaved into a soluble form, sCD40L, which contributes to systemic inflammatory and cardiovascular diseases, and induces survival signals in the absence of protein synthesis block, suggesting a deleterious side effect of CD40L gene therapy. We generated a plasmid encoding non-cleavable human CD40L mutant (pcDNA3.1+-CD40L-M) to determine the direct anti-proliferative and pro-apoptotic effects in CD40-positive lung adenocarcinoma cell line A549, to verify activation of immature dentritic cells (DCs) by co-cultivation with the transfected A549 cells and to evaluate the lower expression of sCD40L relative to that of wild-type CD40L (CD40L-WT) transfectant in cell-free supernatants. These studies suggest that gene transfer of the membrane-stable CD40L mutant into CD40-positive cells may provide an efficient and safe method to treat non-small cell lung cancer.