Pigment epithelium-derived factor (PEDF) is a potent inhibitor of angiogenesis, and the antitumor effect of adeno-associated virus (AAV)-mediated PEDF expression has been demonstrated in a range of animal models. The combined treatment of low-dose
chemotherapy and gene therapy inhibits the growth of solid
tumors more effectively than current traditional
therapies or gene therapy alone. In the present study, the effect of treatment with an AAV2 vector harboring the human PEDF (hPEDF) gene in combination with low-dose
cisplatin on the growth of
Lewis lung carcinoma (LLC) in mice was assessed. LLC cells were infected with AAV-
enhanced green fluorescent protein (EGFP) in the presence or absence of
cisplatin, and then the effect of
cisplatin on AAV-mediated gene expression was evaluated by image and flow cytometric analysis.
Tumor growth, survival time,
vascular endothelial growth factor (
VEGF) expression, microvessel density (MVD) and apoptotic index were analyzed in C57BL/6 mice treated with AAV-hPEDF,
cisplatin or
cisplatin plus AAV-hPEDF. The results of the present study provide evidence that
cisplatin treatment is able to enhance AAV-mediated gene expression in LLC cells. In addition, the combined treatment of
cisplatin plus AAV‑hPEDF markedly prolonged the survival time of the mice and inhibited
tumor growth, resulting in significant suppression of
tumor angiogenesis and induction of
tumor apoptosis in vivo, and also protected against
cisplatin-related toxicity. These findings suggest that combination of AAV-hPEDF and
cisplatin has potential as a novel therapeutic strategy for
lung cancer.