title: P7 peptides targeting bFGF sensitize colorectal cancer cells to CPT-11.
abstract: 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.
authors.affiliation: Institute of Tissue Transplantation and Immunology, Jinan University, Guangzhou, Guangdong, P.R. China.
authors.forename: Wu
authors.initials: W
authors.lastname: Luo
authors.forename: Yonglin
authors.initials: Y
authors.lastname: Yu
authors.forename: Ruixue
authors.initials: R
authors.lastname: Wang
authors.forename: Dan
authors.initials: D
authors.lastname: He
authors.forename: Cong
authors.initials: C
authors.lastname: Wang
authors.forename: Xiangfeng
authors.initials: X
authors.lastname: Zeng
authors.forename: Xilei
authors.initials: X
authors.lastname: Chen
authors.forename: Xiangpeng
authors.initials: X
authors.lastname: Tan
authors.forename: Tao
authors.initials: T
authors.lastname: Huang
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Wu
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology*; D015536:Down-Regulation; D019008:Drug Resistance, Neoplasm; D016222:Fibroblast Growth Factor 2 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019073:HT29 Cells; D006801:Humans; D000077146:Irinotecan; D053533:Keratin-8 / Q000235:genetics / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D012264:Ribonucleotide Reductases / Q000494:pharmacology*; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C494826:BAX protein, human; D053533:Keratin-8; D010446:Peptide Fragments; C419399:acetyl-phenylalanyl-threonyl-leucyl-aspartyl-alanyl-aspartyl-phenylalanine; D051028:bcl-2-Associated X Protein; D016222:Fibroblast Growth Factor 2; D000077146:Irinotecan; D012264:Ribonucleotide Reductases; D051057:Proto-Oncogene Proteins c-akt; D002166:Camptothecin