Related Experiment Videos
Megestrol acetate antagonizes cisplatin cytotoxicity
1Department of Urology, National Taiwan University Medical College, Taipei, ROC.
Anti-Cancer Drugs
|November 21, 1998
Summary
Megestrol acetate (MGA) may reduce the effectiveness of cisplatin chemotherapy by increasing the body's natural defenses against the drug. This suggests MGA could negatively impact tumor response when used with cisplatin.
Area of Science:
- Oncology
- Pharmacology
- Biochemistry
Background:
- Megestrol acetate (MGA) is commonly used to improve appetite in cancer patients undergoing chemotherapy, particularly with cisplatin.
- The impact of MGA on cisplatin's effectiveness against cancer cells is not well understood.
Purpose of the Study:
- To investigate the combined effects of MGA and cisplatin on transitional carcinoma cell lines.
- To explore how MGA influences cisplatin detoxification mechanisms.
Main Methods:
- Utilized two transitional carcinoma cell lines (cisplatin-sensitive NTUB1 and resistant NTUB1/P).
- Assayed combined MGA and cisplatin effects using microculture chemosensitivity.
- Measured changes in metallothionein (MT), glutathione S-transferase-pi (GST-pi), and glutathione (GSH) levels.
Main Results:
- MGA treatment increased cisplatin's IC50 (reduced cytotoxicity) by 1.4-fold in NTUB1 and 1.6-fold in NTUB1/P cells.
- MGA significantly upregulated MT transcript levels in both cell lines.
- Cellular GSH content increased in resistant NTUB1/P cells but not in sensitive NTUB1 cells after MGA exposure.
Conclusions:
- MGA may antagonize cisplatin cytotoxicity by upregulating cellular metallothionein (MT) and glutathione (GSH) levels.
- Concurrent use of MGA with cisplatin-containing chemotherapy might diminish the antitumor activity of cisplatin, potentially impairing treatment outcomes.