Anti-cancer effects of trypsin inhibitor targeting colorectal cancer cell surface GRP78

• 1、The Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Institute of Biotechnology, Shanxi University, TaiYuan 030006
• 2、The Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Institute of Biotechnology, Shanxi University, Taiyuan, 030006

Abstract： Objective The aim of this study was to construct the active fragment of recombinant trypsin inhibitor GBP-TI, which targets tumor cell surface glucose-regulated protein 78 (GRP78), and to investigate its molecular targeting effects on colorectal cancer cells. Methods To construct the GBP-TI expressing vector, the primer containing the expressed sequence of GRP78 binding peptide (GBP) was used to amplify the trypsin inhibitor active fragment (TI); GBP-TI protein was purified by GST-affinity chromatography; The interaction of GBP-TI with cell surface GRP78 was confirmed by confocal immunofluorescence analysis. The effects of GBP-TI on cell survival and apoptosis were detected by MTT and DAPI staining, respectively. Results GBP-TI was able to interact with colorectal cancer cell surface GRP78. In contrast to GST-TI, GBP-TI could induce apoptosis in colorectal cancer cells in a dose-dependent manner, but had a negligible effect on the growth of normal cells. Conclusion GBP-TI can specifically kill tumor cells through binding to cell surface GRP78. This study provides a new strategy for targeted cancer therapy.

Keywords： The trypsin inhibitor glucose regulated protein 78 colon cancer targeted drugs