Modification of IL-24 by tumor penetrating peptide iRGD enhanced its antitumor efficacy against non-small cell lung cancer

Abstract

Interleukin-24 (IL-24) is known for its tumor suppressive activity and the selective induction of apoptosis of numerous human cancer cells, while demonstrating little harm to normal cells. However, poor tumor penetration remains a key problem for the efficacy of IL-24 as a treatment. The iRGD (CRGDK/RGPDC) is a novel tumor-specific peptide with unique tumor-penetrating and cell-internalizing properties. To enhance the tumor-penetrating effects of IL-24, the iRGD peptide was fused with the C-terminal domain of IL-24 to generate a novel recombinant protein, IL-24-iRGD. The aim of the present study was to investigate the antitumor effects of IL-24-iRGD in non-small cell lung cancer (NSCLC) cells in vitro and in vivo. It was observed that IL-24-iRGD increased the production of IL-6, TNF-α and INF-γ from human peripheral blood monocyte (PBMC), and suppressed cell growth of A549 in vitro. Then A549 cells were subcutaneously injected into nude mice, and these tumor-bearing mice were immunized with IL-24, IL-24-iRGD or PBS via the tail vein. The IL-24 and IL-24-iRGD-treated groups exhibited tumor growth inhibition rates of 26.2% and 59.1%, respectively, when compared with the PBS-treated group. Protein penetration into tumors was analyzed by immunofluorescence, cell apoptosis was examined by TdT-mediated dUTP nick end labeling, and the expression of cleaved caspase-3 was analyzed by immuno-histochemical staining. The results demonstrated that IL-24-iRGD induced apoptosis and inhibited the growth of A549 cells to a significantly greater extent when compared with IL-24 treatment alone. It may provide an improved strategy for antitumor therapy and the clinical treatment of NSCLC.

Keywords: A549; Interleukin-24; Non-small cell lung cancer; Tumor-penetrating peptide; iRGD.