A tumor-penetrating peptide modification enhances the antitumor activity of thymosin alpha 1.

ABSTRACT: A serious limitation of numerous antitumor drugs is the incapacity to penetrate solid tumors. However, addition of an RGD fragment to peptide drugs might solve this problem. In this study, we explored whether the introduction of a permeability-enhancing sequence, such as iRGD (CRGDK/RGPD/EC) fragments, would enhance the activity of thymosin alpha 1 (T?1). The modified T?1 (T?1-iRGD) was successfully expressed and purified, and the in vitro assay showed that T?1-iRGD presented a similar activity as T?1 in promoting proliferation of mouse splenocytes. Meanwhile, cell adhesion analysis revealed that T?1-iRGD exhibited more specific and greater binding with tumor cells compared with T?1. Furthermore, the iRGD fragment evidently enhanced the basal ability of T?1 to inhibit proliferation of cancer cells in vitro, particularly of mouse melanoma cell line B16F10 and human lung cancer cell line H460. Our findings indicated that the addition of an iRGD fragment increased the anti-proliferative activity of T?1 against cancer cells by improving the ability of T?1 to penetrate the tumor cells. This study highlighted the important roles of an iRGD sequence in the therapeutic strategy of T?1-iRGD. Thus, T?1-iRGD could be a novel drug candidate for cancer treatment.

SUBMITTER: Lao X 

PROVIDER: S-EPMC3747120 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature