Lovastatin Potentiates Antitumor Activity and Attenuates Cardiotoxicity of Doxorubicin in Three Tumor Models in Mice

• Published in: Clinical cancer research 2000-05, Vol.6 (5), p.2044
• Main Authors: Feleszko, W, Mlynarczuk, I, Balkowiec-Iskra, E Z, Czajka, A, Switaj, T, Stoklosa, T, Giermasz, A, Jakóbisiak, M
• Format: Article
• Language: English
• Subjects: 3T3 Cells; Animals; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Cell Division - drug effects; Cell Line, Transformed; Cell Survival - drug effects; Disease Models, Animal; Dose-Response Relationship, Drug; Doxorubicin - administration & dosage; Doxorubicin - adverse effects; Doxorubicin - pharmacology; Drug Resistance, Neoplasm; Drug Synergism; Female; Heart Diseases - blood; Heart Diseases - chemically induced; Heart Diseases - prevention & control; Lovastatin - administration & dosage; Lovastatin - pharmacology; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Inbred DBA; Neoplasm Transplantation; Neoplasms, Experimental - blood; Neoplasms, Experimental - drug therapy; Neoplasms, Experimental - pathology; Time Factors; Troponin T - blood; Troponin T - drug effects; Tumor Cells, Cultured
• ISSN: 1078-0432; 1557-3265

Lovastatin, a drug commonly used in the clinic to treat hypercholesterolemia, has previously been reported to exert antitumor effects in rodent tumor models and to strengthen the antitumor effects of immune response modifiers (tumor necrosis factor α and IFN-γ) or chemotherapeutic drugs (cisplatin). In the present report, we show in three murine tumor cell lines (Colon-26 cells, v-Ha- ras -transformed NIH-3T3 sarcoma cells, and Lewis lung carcinoma cells) that lovastatin can also effectively potentiate the cytostatic/cytotoxic activity of doxorubicin. In three tumor models (Colon-26 cells, v-Ha- ras -transformed NIH-3T3 sarcoma cells, and Lewis lung carcinoma cells) in vivo , we have demonstrated significantly increased sensitivity to the combined treatment with both lovastatin (15 mg/kg for 10 days) and doxorubicin (3 × 2.5 mg/kg; cumulative dose, 7.5 mg/kg) as compared with either agent acting alone. Lovastatin treatment also resulted in a significant reduction of troponin T release by cardiomyocytes in doxorubicin-treated mice. This observation is particularly interesting because lovastatin is known to reduce doxorubicin-induced cardiac injury.