In vivo evidence of duality effects for lovastatin in a nude mouse cancer model.
Statins, hydroxy-methyl-glutaryl coenzyme A reductase inhibitors, are the most effective medication for lowering cholesterol, cardiovascular morbidity and mortality. On the basis of our previous in vitro experimental results on an anaplastic thyroid cancer cell line, we designed a nude mouse model in which cancer cells were seeded subcutaneously to examine the potential anticancer effects of lovastatin in vivo. As expected, tumor growth was significantly reduced in the mice treated with 5 or 10 mg/kg/day of lovastatin compared with the positive control group. However, the tumor grew much faster in the mice treated with 1 mg/kg/day of lovastatin than in the positive control group. We suspect this result might be related to vascular endothelial growth factor. In this model, we found that lovastatin inhibits tumor growth at a high dosage (5 or 10 mg/kg/day), suggesting it could be used as an effectively adjuvant chemotherapy for cancer. However, it also promotes tumor growth at a low dosage (1 mg/kg/day). This duality effect should be further studied for patients treated with various dosages of statins.
Wang
Chih-Yuan
CY
Department of Internal Medicine, Far-Eastern Memorial Hospital, Institute of Medical Science, Taipei Hsien, Taiwan.
Shui
Hao-Ai
HA
Chang
Tien-Chun
TC
D000818:Animals; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D007150:Immunohistochemistry; D008148:Lovastatin / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D040262:Receptors, Vascular Endothelial Growth Factor / Q000378:metabolism; D013964:Thyroid Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016896:Treatment Outcome; D047368:Tumor Burden / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D042461:Vascular Endothelial Growth Factor A; D008148:Lovastatin; D040262:Receptors, Vascular Endothelial Growth Factor