期刊
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
卷 33, 期 1, 页码 194-200出版社
SPANDIDOS PUBL LTD
DOI: 10.3892/ijmm.2013.1547
关键词
basic fibroblast growth factor; drug resistance; apoptosis; colorectal cancer
资金
- National Natural Science Foundation of China [81071800, 30973671]
- Guangdong Provincial Science and Technology Program [2010B060900040]
- Natural Science Foundation of Guangdong Province of China [9151064001000031]
- Natural Science Foundation of Zhejiang Province of China [Y2110492]
- Science and Technology Planning Project of Wenzhou [Y20090244]
- Fundamental Research Funds for the Central Universities
- Guangdong Provincial 'Thousand-Hundred-Ten Talent Project'
- Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, Jinan University
The low survival rate of patients with colorectal cancer (CRC) is mainly due to the drug resistance of tumor cells to chemotherapeutic agents. It has been reported that basic fibroblast growth factor (bFGF) is an essential factor involved in the epigenetic mechanisms of drug resistance, which provides a novel potential target for improving the sensitivity of tumor cells to chemotherapeutic agents. In this study, we first demonstrate that a novel bFGF antagonist, peptide P7, previously isolated by phage display technology, reversed bFGF-induced resistance to irinotecan hydrochloride (CPT-11), and counteracted the anti-apoptotic effects of bFGF on CPT-11-treated HT-29 cells. Further experiments indicated that the inhibition of Akt activation, the suppression of bFGF internalization, the increase in the Bax to Bcl-2 ratio and the downregulation of cytokeratin 8 (CK8) by P7 may contribute to the counteracting of the anti-apoptotic effects of bFGF, and further reversal of bFGF-induced resistance to CPT-11. Our results suggest that peptide P7 may have therapeutic potential in CRC as a sensitizer to chemotherapeutic agents by targeting bFGF.
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