title: 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 (Tα1). The modified Tα1 (Tα1-iRGD) was successfully expressed and purified, and the in vitro assay showed that Tα1-iRGD presented a similar activity as Tα1 in promoting proliferation of mouse splenocytes. Meanwhile, cell adhesion analysis revealed that Tα1-iRGD exhibited more specific and greater binding with tumor cells compared with Tα1. Furthermore, the iRGD fragment evidently enhanced the basal ability of Tα1 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 Tα1 against cancer cells by improving the ability of Tα1 to penetrate the tumor cells. This study highlighted the important roles of an iRGD sequence in the therapeutic strategy of Tα1-iRGD. Thus, Tα1-iRGD could be a novel drug candidate for cancer treatment.
authors: Department of Life Science and Technology, China Pharmaceutical University, Nanjing, Jiang Su Province, PR China.
authors: Xingzhen
authors: X
authors: Lao
authors: Meng
authors: M
authors: Liu
authors: Jiao
authors: J
authors: Chen
authors: Heng
authors: H
authors: Zheng
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000378:metabolism; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects; D008546:Melanoma, Experimental / Q000188:drug therapy; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism*; D010539:Permeability; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D013154:Spleen / Q000166:cytology / Q000187:drug effects; D000077596:Thymalfasin; D013947:Thymosin / Q000031:analogs & derivatives* / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D039302:Integrin alphaVbeta3; D009842:Oligopeptides; D011993:Recombinant Fusion Proteins; D013947:Thymosin; C047981:arginyl-glycyl-aspartic acid; D000077596:Thymalfasin
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