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Identification Keratin 1 as a cDDP-resistant protein in nasopharyngeal carcinoma cell lines
Sanyuan Tang1, Weiguo Huang, Meizuo Zhong
1Department of Oncology, Xiangya Hospital, Central South University, Changsha 410008, P. R. China.
Abstract:
Multidrug resistance (MDR) to anticancer drugs is a major obstacle to successful chemotherapy of tumors. Understanding the molecular basis to chemoresistance is likely to provide better treatment. Cell lines resistant to cis-diamminedichloroplatinum (CNE2/cDDP) were established from human nasopharyngeal carcinoma (NPC) cell lines CNE2. Comparative proteomics involving 2-dimensional gel electrophoresis (2-DE) and ESI-Q-TOF-MS were performed on protein extracted from CNE2 and CNE2/cDDP cell lines to screen drug resistance-related proteins. Keratin 1 (KRT1), cathepsin D (CTSD) and annexin a5 (ANXA5) were identified as three proteins showing higher expression in CNE2/cDDP compared to CNE2. Furthermore, suppression of KRT1 expression by siRNA resulted in decreased MDR in siRNA-CNE2/cDDP cells. And upregulation of KRT1 could result in increased of drug resistance in NPC cell lines. Taken together, KRT1 protein and its activity levels were higher in cDDP-resistant NPC cell lines compared to their parental cell lines. These data clearly linked KRT1 and cDDP resistance mechanisms. KRT1 could serve as a biomarker for chemotherapy sensitivity of NPC.
Insights
Multidrug resistance (MDR) in nasopharyngeal carcinoma (NPC) is a major chemotherapy challenge. Keratin 1 (KRT1) was identified as a key protein linked to cisplatin resistance, potentially serving as a biomarker for treatment sensitivity.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Multidrug resistance (MDR) to anticancer drugs impedes effective chemotherapy.
- Understanding chemoresistance mechanisms is crucial for improving cancer treatment outcomes.
Purpose of the Study:
- To identify proteins associated with cisplatin resistance in human nasopharyngeal carcinoma (NPC) cells.
- To investigate the role of identified proteins in MDR and their potential as therapeutic biomarkers.
Main Methods:
- Establishment of cisplatin-resistant NPC cell lines (CNE2/cDDP) from parental CNE2 cells.
- Comparative proteomics using 2-dimensional gel electrophoresis (2-DE) and ESI-Q-TOF-MS to analyze protein expression differences.
- Gene silencing using siRNA to assess the functional impact of Keratin 1 (KRT1) on drug resistance.
Main Results:
- Keratin 1 (KRT1), cathepsin D (CTSD), and annexin A5 (ANXA5) were found to be upregulated in cisplatin-resistant NPC cells.
- Suppression of KRT1 expression using siRNA led to a decrease in MDR.
- Upregulation of KRT1 correlated with increased drug resistance in NPC cell lines.
Conclusions:
- Keratin 1 (KRT1) plays a significant role in the mechanism of cisplatin resistance in NPC.
- Elevated KRT1 levels are associated with chemoresistance, suggesting KRT1 as a potential biomarker for chemotherapy sensitivity in NPC.
