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[The effect of ginkgolic acids on multidrug resistance in oral squamous cell carcinoma]
Hui Wang1, Chen-Chen Zhou, Yun Feng
1State Key Laboratory of Oral Diseases, Sichuan University, Chengdu 610041, China.
Objective:
Carboplatin (CBP)-resistant cell line (Tca8113/CBP) and pingyangmycin (PYM)-resistant cell line (Tca8113/PYM) were established in vitro. Ginkgolic acids' influence over multidrug resistance (MDR) of drug-resistant cells was discussed by ginkgolic acids coupled with chemotherapy drugs.
Methods:
The expression of P-glycoprotein (P-gp) was detected by immunohistochemistry. MTT assay was applied to ascertain the resistance index of drug-resistant cells. The effect of different concentrations of ginkgolic acids on the proliferation of drug-resistant cells and parental cell was measured by MTT assay. Making sure the non-toxic concentration of ginkgolic acids and observing the reversal effect of ginkgolic acids on drug-resistant cells. Resistance index was redetermined by MTT assay after ginkgolic acids coupled with chemotherapy drugs induced the cell lines for some time.
Results:
Immunohistochemistry showed that P-gp positive expression rate of drug-resistant cells was significantly higher than parental cells. The non-toxic concentration of ginkgolic acids which was determined by MTT assay was 10 microg x mL(-1). The reversal folds of Tca8113/CBP cell line to CBP and Tca8113/PYM cell line to PYM were 2.94 and 2.43 respectively. Before coupled with ginkgolic acids, the resistance indices of Tca8113/CBP and Tca8113/PYM cell lines were 3.24 and 11.9 respectively. When ginkgolic acids was added with chemotherapy drugs for some time, the resistance indices of Tca8113/CBP and Tca8113/PYM cell lines were 2.18 and 4.43 respectively.
Conclusion:
This experiment successfully induced the drug-resistant cell lines of Tca8113/CBP and Tca8113/PYM. The method of chemotherapy drugs coupled with ginkgolic acids further confirmed the effect on proliferation of Tca8113/CBP and Tca8113/PYM cell lines was reducing. Non-toxic concentration of ginkgolic acids can partially reverse the drug resistance of Tca8113/ CBP and Tca8113/PYM cell lines. Furthermore, MDR level of drug-resistant cells decreased somewhat when they were induced by ginkgolic acids coupled with chemotherapy drugs for some time.
Insights
Ginkgolic acids partially reverse multidrug resistance (MDR) in carboplatin and pingyangmycin-resistant cancer cells. This study demonstrates ginkgolic acids
Area of Science:
- Oncology
- Pharmacology
- Cell Biology
Background:
- Multidrug resistance (MDR) is a major challenge in cancer chemotherapy, limiting the efficacy of drugs like carboplatin (CBP) and pingyangmycin (PYM).
- Drug-resistant cell lines, such as Tca8113/CBP and Tca8113/PYM, are crucial for studying MDR mechanisms and evaluating potential therapeutic strategies.
Purpose of the Study:
- To investigate the influence of ginkgolic acids on multidrug resistance (MDR) in established CBP-resistant (Tca8113/CBP) and PYM-resistant (Tca8113/PYM) cell lines.
- To determine the efficacy of combining ginkgolic acids with chemotherapy drugs in overcoming drug resistance.
Main Methods:
- Establishment of in vitro CBP-resistant (Tca8113/CBP) and PYM-resistant (Tca8113/PYM) cell lines.
- Immunohistochemistry to detect P-glycoprotein (P-gp) expression.
- MTT assays to determine cell proliferation, resistance indices, and non-toxic concentrations of ginkgolic acids.
Main Results:
- Drug-resistant cells exhibited significantly higher P-gp expression compared to parental cells.
- A non-toxic concentration of ginkgolic acids was determined to be 10 microg/mL.
- Ginkgolic acids partially reversed resistance, with reversal folds of 2.94 for Tca8113/CBP and 2.43 for Tca8113/PYM.
- Combined treatment with ginkgolic acids and chemotherapy drugs reduced resistance indices to 2.18 for Tca8113/CBP and 4.43 for Tca8113/PYM.
Conclusions:
- Successfully established CBP- and PYM-resistant cell lines (Tca8113/CBP and Tca8113/PYM).
- Ginkgolic acids, at non-toxic concentrations, can partially reverse drug resistance in these cell lines.
- Combining ginkgolic acids with chemotherapy drugs demonstrates a reduced effect on cancer cell proliferation and a decrease in MDR levels.
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