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[Correlation of protein kinase C isoform expression with multidrug resistance in KBV200 cells]
Ya-Wei Yuan1, Ai-Min Sun, Chuan-Gang Li
1Department of Radiotherapy, Zhujiang Hospital, First Military Medical University, Guangzhou 510282, China. ywyuan@163.net
Objective:
To investigate the association of protein kinase C (PKC) isoforms and multidrug resistance (MDR) mechanism in KBV200 cells.
Methods:
Western blotting was utilized to examine the expression and subcellular distribution of PKC isoforms were measured in KBV200 cells with MDR and drug-sensitive KB cells, and the fluorescence intensity of PKC isoforms was detected by flow cytometry (FCM).
Results:
KBV200 cells possessed higher PKC activities, with increased percentage of membrane fraction. As compared with parental KB cells, the expression of PKCalpha was significantly increased in KBV200 cells, while PKCbeta and epsilon expressions remained unchanged, and PKCgamma and zeta failed to be detected. Fluorescence intensity of PKCalpha in KBV200 cells was increased.
Conclusion:
PKC might contribute to MDR phenotype in KBV200 cells, and of the isoforms so far detected, PKCalpha might play an important role in MDR phenotype.
Insights
Protein kinase C (PKC) may contribute to multidrug resistance (MDR) in KBV200 cells. Specifically, increased PKCalpha expression and activity appear to play a significant role in this MDR phenotype.
Area of Science:
- Biochemistry
- Cell Biology
- Molecular Pharmacology
Context:
- Multidrug resistance (MDR) is a significant challenge in cancer chemotherapy.
- KBV200 cells exhibit a multidrug-resistant phenotype.
- Protein kinase C (PKC) signaling pathways are implicated in various cellular processes, including drug resistance.
Purpose:
- To investigate the association between specific protein kinase C (PKC) isoforms and the multidrug resistance (MDR) mechanism in KBV200 cells.
- To compare the expression and subcellular localization of PKC isoforms in drug-resistant KBV200 cells versus drug-sensitive parental KB cells.
Summary:
- Western blotting and flow cytometry revealed higher PKC activity and an increased percentage of membrane-bound PKC in KBV200 cells.
- PKCalpha expression was significantly elevated in KBV200 cells compared to parental KB cells, with unchanged PKCbeta and epsilon levels. PKCgamma and zeta were undetectable.
- Increased fluorescence intensity of PKCalpha was observed in KBV200 cells, suggesting enhanced activity and membrane localization.
Impact:
- These findings suggest that PKC signaling, particularly the PKCalpha isoform, may contribute to the development of the multidrug resistance (MDR) phenotype in KBV200 cells.
- Understanding the role of PKCalpha in MDR could offer potential therapeutic targets for overcoming drug resistance in cancer treatment.