Research Papers:
Poly(C)-binding protein 1 mediates drug resistance in colorectal cancer
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Abstract
Jiani Guo1,*, Changli Zhu1,*, Kangqun Yang2,*, Jin Li1, Nan Du1, Mingzhu Zong1, Jianwei Zhou3, Jingdong He1
1Department of Oncology, Huai’an First People’s Hospital, Nanjing Medical University, Huai’an, Jiangsu Province, China
2Department of Pharmacy, Huai’an First People’s Hospital, Nanjing Medical University, Huai’an, Jiangsu Province, China
3Department of Molecular Cell Biology and Toxicology, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Cancer Center, Nanjing Medical University, Nanjing, China
*These authors contributed equally to this work
Correspondence to:
Jingdong He, email: [email protected]
Keywords: poly(C)-binding protein 1, colorectal cancer, chemoresistance, oxaliplatin
Received: September 02, 2016 Accepted: December 27, 2016 Published: January 05, 2017
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.
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