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[Correlation of protein kinase C activity and its subcellular distrubution with multidrug resistance in KVB200 cells]
Ai-Min Sun1, Ya-Wei Yuan, Chuan-Gang Li
1Department of Radiotherapy, Zhujiang Hospital, First Military Medical University, Guangzhou 510282, China. sunaimin70@263.net
Objective:
To investigate the relationship between protein kinase C (PKC) and multidrug resistance (MDR) in cancer cell line KBV200.
Methods:
MTT assay was used to evaluate the IC50 of vincristine (VCR) and adriamycin (ADR) in KB cell line and its VCR-resistant derivative KBV200 cells. PKC activities in the 2 cell lines were assayed by measuring the incorporation of (32)P from [gamma-(32)P] ATP into the peptide substrates.
Results:
The IC50 values of VCR and ADR in KBV200 cells was 64.03 and 18.8 folds greater than those in KB cells. PKC activities of the membrane and cytosol fraction in KBV200 cells were increased compared with that in KB cells, with the total PKC activity 1.12-fold higher. Phorbol-12-myristate-13 -acetate increased PKC activity of the membrane fraction and IC50 values of KBV200 cells, while staurosporine worked to the opposite effects.
Conclusion:
PKC may contribute to MDR mechanism in KBV200 cells.
Insights
Protein kinase C (PKC) activity is elevated in multidrug-resistant (MDR) KBV200 cancer cells. This suggests PKC plays a role in the MDR mechanism, impacting drug resistance to vincristine and adriamycin.
Area of Science:
- Biochemistry
- Molecular Biology
- Cancer Research
Context:
- Multidrug resistance (MDR) is a significant challenge in cancer chemotherapy.
- Cancer cell lines like KBV200 develop resistance to multiple chemotherapeutic agents.
- Protein kinase C (PKC) is a family of enzymes involved in various cellular processes.
Purpose:
- To investigate the potential role of protein kinase C (PKC) in the development of multidrug resistance (MDR).
- To examine the relationship between PKC activity and resistance to vincristine (VCR) and adriamycin (ADR) in the KBV200 cancer cell line.
Summary:
- KBV200 cells, a VCR-resistant derivative of KB cells, exhibited significantly higher IC50 values for VCR and ADR.
- Increased PKC activity was observed in both membrane and cytosol fractions of KBV200 cells compared to KB cells.
- Modulation of PKC activity using phorbol-12-myristate-13-acetate and staurosporine affected drug resistance in KBV200 cells, supporting PKC's involvement.
Impact:
- Findings suggest that PKC is a potential contributor to the MDR mechanism in KBV200 cells.
- This research may inform the development of novel therapeutic strategies to overcome drug resistance in cancer.
- Understanding the role of PKC in MDR could lead to targeted interventions to enhance chemotherapy efficacy.