[Reversal of multidrug resistance of MCF-7/ADR in nude mice by grape seed polyphenol]
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Cui-Juan Zhang1, Geng-Yin Zhou, Li Li
1Department of Pathology, Medical School of Shandong University, Jinan 250012, China.
Objective:
To study the reversing effect of Grape seed polyphenol (GSP) on multidrug resistance of MCF-7/ADR cell in vivo.
Methods:
The transplantable breast carcinoma cell line MCF-7/ADR model was established in BALB/C-nu/nu mice by subcutaneous implantation. Flow cytometry (FCM) was used to investigate the changes of Pgp expression and apoptosis rate after different drug treatment.
Results:
GSP has some effect on inhibition of tumor growth (the rate of inhibition was 18.35%), and combined with adriamycin can significantly inhibit tumor growth in nude mice, 20 mg/kg GSP can effectively reverse the resistance of MCF-7/ADR cells to ADR in vivo, and the rate of inhibition was 54.64%. FCM results showed that the expression of Pgp was significantly decreased (32.03 +/- 2.09) After administration of GSP and ADR, there was distinct difference between it and control (55.13 +/- 2.12). The mean rate of apoptosis was 15.12% +/- 1.04%, and was significantly increased compared with control (9.07% +/- 0.43%), P < 0.05.
Conclusion:
GSP can effectively reversed the resistance of MCF-7/ADR cells in nude mice, the mechanism may be correlated with inhibition of Pgp expression and apoptosis.
Insights
Grape seed polyphenol (GSP) reverses multidrug resistance in breast cancer cells in vivo. GSP inhibits P-glycoprotein (Pgp) expression and increases apoptosis, enhancing adriamycin efficacy.
Area of Science:
- Pharmacology and Toxicology
- Cancer Research
- Natural Products Chemistry
Background:
- Multidrug resistance (MDR) is a major challenge in cancer chemotherapy, limiting treatment efficacy.
- MCF-7/ADR cells exhibit resistance to adriamycin (ADR), a common chemotherapeutic agent.
- Grape seed polyphenol (GSP) is a natural compound with potential therapeutic properties.
Purpose of the Study:
- To investigate the in vivo reversing effect of Grape seed polyphenol (GSP) on multidrug resistance.
- To evaluate GSP's impact on MCF-7/ADR cell resistance to adriamycin (ADR).
- To explore the underlying mechanisms of GSP's action on drug resistance.
Main Methods:
- Establishment of a transplantable breast carcinoma MCF-7/ADR cell model in BALB/C-nu/nu mice.
- Subcutaneous implantation of tumor cells to create an in vivo model.
- Flow cytometry (FCM) analysis to assess P-glycoprotein (Pgp) expression and apoptosis rates.
Main Results:
- GSP demonstrated a 18.35% inhibition of tumor growth.
- Combined GSP and adriamycin significantly inhibited tumor growth (54.64% inhibition rate).
- GSP treatment significantly decreased Pgp expression (32.03% vs. 55.13% in control) and increased apoptosis (15.12% vs. 9.07% in control).
Conclusions:
- Grape seed polyphenol (GSP) effectively reverses adriamycin (ADR) resistance in MCF-7/ADR cells in vivo.
- The mechanism involves the inhibition of P-glycoprotein (Pgp) expression.
- GSP also enhances apoptosis, contributing to its chemosensitizing effect.
