Inhibition of lung tumor cell growth in vitro and mouse lung tumor formation by lovastatin.

Abstract

The HMG-CoA reductase inhibitor, lovastatin (LOV), has been reported to inhibit Ras farnesylation and the growth of Ras-transformed cells. Mouse lung tumors and human lung adenocarcinomas often have activating mutations in K-ras alleles. In the present study, we determined whether LOV inhibited the growth in vitro of mouse (C10, E9, LM1, LM2, and 82-132) and human (NCl-H125, H292, H441, H460, and H661) nor-transformed and neoplastically transformed lung epithelial cells and whether growth inhibition was related to cell transformation or K-ras activation. LOV inhibited the growth of mouse and human lung cells, but cell sensitivities were unrelated to neoplastic transformation or K-ras mutation. In addition, we evaluated whether LOV could inhibit the formation of lung adenomas induced by the tobacco-specific nitrosamine, 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in mice. LOV was administered in the diet at 0, 40, 160, or 400 ppm ad libitum to male strain A/J mice beginning 1 week after lung tumor induction with NNK (10 mumol/mouse). Mice were euthanized 6 months later. Enumeration of lung tumors revealed that LOV did not affect tumor incidence or size, but significantly reduced tumor multiplicity in a dose-related manner. These data suggest that LOV can suppress the formation of NNK-induced lung tumors, possibly at an early promotional stage. This suppression does not appear to be related to either the presence of mutated K-ras or to changes in K-ras expression.

• Authors: M A Hawk, K T Cesen, J C Siglin, G D Stoner, R J Ruch
• Journal: Cancer letters (Cancer Lett) Vol. 109 Issue 1-2 Pg. 217-22 (Dec 03 1996) ISSN: 0304-3835 [Print] Ireland
• PMID: 9020924 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antineoplastic Agents
• Carcinogens
• Nitrosamines
• 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone
• Lovastatin

Topics

• Animals
• Antineoplastic Agents (therapeutic use)
• Carcinogens
• Cell Division (drug effects)
• Drug Screening Assays, Antitumor
• Humans
• Lovastatin (therapeutic use)
• Lung Neoplasms (chemically induced, pathology, prevention & control)
• Male
• Mice
• Mice, Inbred A
• Nitrosamines
• Tumor Cells, Cultured (drug effects)