Tumor-Penetrating Peptide Enhances Antitumor Effects of IL-24 Against Prostate Cancer

Abstract

The interleukin-24 (IL-24), a member of the IL-10–related cytokine gene family, is well known for its tumor suppressor activity in a broad spectrum of human tumors without damaging normal cells. However, poor tumor penetration remains a key problem for the efficacy of IL-24 as a treatment. iRGD is a novel tumor-specific peptide with unique tumor-penetrating and cell-internalizing properties. To enhance the tumor-penetrating and antitumor effects of IL-24, we engineered a recombinant protein consisting of the IL-24 fused to iRGD, which was named IL-24-iRGD. The aim of the present study was to investigate the antitumor effects of IL-24-iRGD in prostate cancer cells in vitro and in vivo. It was observed that IL-24-iRGD induced cell apoptosis, suppressed cell growth of PC-3 in vitro, and promoted protein penetration into tumors in vivo, whereas it had no effect on normal cell line RWPE-1. Then, PC-3 cells were subcutaneously injected into nude mice, and these tumor-bearing mice were administered 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 38.6% and 65.6%, respectively, when compared with the PBS-treated group. Besides, cell apoptosis was examined by TdT-mediated dUTP nick end labeling, and the expression of cleaved caspase-3 was analyzed by immunohistochemical staining. The results demonstrated that IL-24-iRGD induced apoptosis and inhibited the growth of PC-3 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 prostate cancer.