title: Poly(C)-binding protein 1 mediates drug resistance in colorectal cancer.
abstract: Oxaliplatin (L-OHP) is standard treatment for colorectal cancer. However, resistance to L-OHP often leads to treatment failure or cancer relapse. Understanding of the mechanism underlying L-OHP resistance is important to overcome the resistance and improve colorectal cancer treatment. This study aimed to identify new proteins that mediates L-OHP resistance in colorectal cancer and elucidate their mode of function. HT-29 cells were exposed to gradually increased concentration of L-OHP to select L-OHP resistant HT-29/L-OHP cell line. Proteomic analysis of HT-29 and HT-29/L-OHP cells were performed to identify differentially expressed proteins, including Poly(C)-binding protein 1 (PCBP1). PCBP1 expression level in 20 cases of L-OHP sensitive patients and 20 cases of L-OHP refractory patients was analyzed by immunohistochemistry. Chemoresistance and Akt activation in HT-29 and HT-29/L-OHP cells were analyzed by MTT assay and Western blot analysis. We identified 37 proteins showing differential expression in HT-29/L-OHP and HT-29 cells. In particular, PCBP1 protein level increased 15.6 fold in HT-29/L-OHP cells compared to HT-29 cells. Knockdown of PCBP1 sensitized HT-29/L-OHP and HT-29 cells to L-OHP, while overexpression of PCBP1 increased L-OHP resistance in HT-29 cells. In addition, PCBP1 expression was significantly higher in tumor samples from L-OHP refractory patients than in those from L-OHP responsive patients. Furthermore, we found that knockdown of PCBP1 inhibited the activation of Akt in HT-29/L-OHP and HT-29 cells. In conclusion, our findings suggest that PCBP1 is a molecular marker of L-OHP resistance in colorectal cancer and a promising target for colorectal cancer therapy.
authors.affiliation: Department of Oncology, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu Province, China.
authors.forename: Jiani
authors.initials: J
authors.lastname: Guo
authors.affiliation: Department of Oncology, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu Province, China.
authors.forename: Changli
authors.initials: C
authors.lastname: Zhu
authors.affiliation: Department of Pharmacy, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu Province, China.
authors.forename: Kangqun
authors.initials: K
authors.lastname: Yang
authors.affiliation: Department of Oncology, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu Province, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Oncology, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu Province, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Du
authors.affiliation: Department of Oncology, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu Province, China.
authors.forename: Mingzhu
authors.initials: M
authors.lastname: Zong
authors.affiliation: Department of Molecular Cell Biology and Toxicology, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Cancer Center, Nanjing Medical University, Nanjing, China.
authors.forename: Jianwei
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Oncology, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu Province, China.
authors.forename: Jingdong
authors.initials: J
authors.lastname: He
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D015153:Blotting, Western; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology*; D004268:DNA-Binding Proteins; D019008:Drug Resistance, Neoplasm / Q000502:physiology*; D015180:Electrophoresis, Gel, Two-Dimensional; D055785:Gene Knockdown Techniques; D019073:HT29 Cells; D034441:Heterogeneous-Nuclear Ribonucleoproteins / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D009944:Organoplatinum Compounds / Q000494:pharmacology; D000077150:Oxaliplatin; D016601:RNA-Binding Proteins; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D009944:Organoplatinum Compounds; C094604:PCBP1 protein, human; D016601:RNA-Binding Proteins; D000077150:Oxaliplatin
keywords: chemoresistance; colorectal cancer; oxaliplatin; poly(C)-binding protein 1