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Updated: Mar 9, 2026
Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms
Published on: December 9, 2015
Poly(C)-binding protein 1 mediates drug resistance in colorectal cancer
Jiani Guo1, Changli Zhu1, Kangqun Yang2
1Department of Oncology, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu Province, China.
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.
Insights
Poly(C)-binding protein 1 (PCBP1) drives oxaliplatin resistance in colorectal cancer. Targeting PCBP1 may overcome treatment failure and improve patient outcomes.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Oxaliplatin (L-OHP) is a cornerstone chemotherapy for colorectal cancer (CRC).
- Acquired resistance to L-OHP significantly limits its therapeutic efficacy, leading to treatment failure and relapse.
- Identifying novel mechanisms and molecular targets is crucial for overcoming L-OHP resistance in CRC.
Purpose of the Study:
- To identify novel proteins mediating L-OHP resistance in colorectal cancer.
- To elucidate the functional role of identified proteins in L-OHP resistance.
- To evaluate the potential of identified proteins as therapeutic targets for overcoming L-OHP resistance.
Main Methods:
- Development of an L-OHP-resistant colorectal cancer cell line (HT-29/L-OHP).
- Proteomic analysis to identify differentially expressed proteins between sensitive and resistant cells.
- Immunohistochemistry to assess protein expression in patient tumor samples.
- Cell viability (MTT assay) and Western blot analysis to evaluate chemoresistance and signaling pathway activation (Akt).
Main Results:
- Proteomic analysis revealed significant differential expression of 37 proteins, with Poly(C)-binding protein 1 (PCBP1) showing a 15.6-fold increase in resistant cells.
- PCBP1 overexpression conferred L-OHP resistance, while PCBP1 knockdown sensitized cells to L-OHP.
- Elevated PCBP1 expression was observed in L-OHP-refractory patient tumors compared to L-OHP-responsive tumors.
- PCBP1 knockdown inhibited Akt activation, a key signaling pathway in cancer progression.
Conclusions:
- PCBP1 is a critical mediator of L-OHP resistance in colorectal cancer.
- PCBP1 serves as a potential molecular marker for predicting L-OHP response.
- Targeting PCBP1 represents a promising therapeutic strategy to overcome L-OHP resistance in CRC.
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