Lovastatin potentiates antitumor activity and attenuates cardiotoxicity ofdoxorubicin in three tumor models in mice

Lovastatin, a drug commonly used in the clinic to treat hypercholesterolemi a, 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 alpha and IFN-gamma) or chemotherapeutic drugs (cis platin). In the present report, we show in three murine tumor cell lines (C olon-26 cells, v-Ha-ras-transformed NIH-3T3 sarcoma cells, and Lewis lung c arcinoma cells) that lovastatin can also effectively potentiate the cytosta tic/cytotoxic activity of doxorubicin, In three tumor models (Colon-26 cell s, v-Ha-ras-transformed NIH-3T3 sarcoma cells, and Lewis lung carcinoma cel ls) in vivo, we have demonstrated significantly increased sensitivity to th e combined treatment with both lovastatin (15 mg/kg for 10 days) and doxoru bicin (3 x 2.5 mg/kg; cumulative dose, 7.5 mg/kg) as compared with either a gent acting alone, Lovastatin treatment also resulted in a significant redu ction 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.