標題: | Potential antitumor therapeutic application of Grimontia hollisae thermostable direct hemolysin mutants |
作者: | Huang, Sheng-Cih Wang, Yu-Kuo Huang, Wan-Ting Kuo, Tsam-Ming Yip, Bak-Sau Li, Tien-Hsiung Thomas Wu, Tung-Kung 生物科技學系 Department of Biological Science and Technology |
關鍵字: | Anticancer;epidermal growth factor receptor;Grimontia hollisae;immunotoxin;thermostable direct hemolysin |
公開日期: | 1-四月-2015 |
摘要: | We report on the preparation of a new type of immunotoxin by conjugation of an epidermal growth factor receptor (EGFR)-binding peptide and an R46E mutation of thermostable direct hemolysin from Grimontia hollisae, (Gh-TDHR46E/EB). The hybrid immunotoxin was purified to homogeneity and showed a single band with slight slower mobility than that of Gh-TDHR46E. Cytotoxicity assay of Gh-TDHR46E/EB on EGFR highly, moderately, low, and non-expressed cells, A431, MDA-MB-231, HeLa, and HEK293 cells, respectively, showed apparent cytotoxicity on A431 and MDA-MB-231 cells but not on HeLa or HEK293 cells. In contrast, no cytotoxicity was observed for these cells treated with either Gh-TDHR46E or EB alone, indicating enhanced cytotoxic efficacy of Gh-TDHR46E by the EGFR binding moiety. Further antitumor activity assay of Gh-TDHR46E/EB in a xenograft model of athymic nude mice showed obvious shrinkage of tumor size and degeneration, necrosis, and lesions of tumor tissues compared to the normal tissues. Therefore, the combination of Gh-TDHR46E with target affinity agents opens new possibilities for pharmacological treatment of cancers and potentiates the anticancer drug's effect. |
URI: | http://dx.doi.org/10.1111/cas.12623 http://hdl.handle.net/11536/124695 |
ISSN: | 1347-9032 |
DOI: | 10.1111/cas.12623 |
期刊: | CANCER SCIENCE |
Volume: | 106 |
Issue: | 4 |
起始頁: | 447 |
結束頁: | 454 |
顯示於類別: | 期刊論文 |