EFFECT OF LOVASTATIN ALONE AND AS AN ADJUVANT CHEMOTHERAPEUTIC AGENT ON HEPATOMA TISSUE CULTURE-4 CELL-GROWTH

Background: Cholesterol is essential for cell viability and growth. In terference with the cholesterol biosynthetic pathway with a 3-hydroxy- 3-methylglutaryl coenzyme A reductase inhibitor (e.g., lovastatin) may preferentially slow malignant cell growth and offer a new approach to cancer chemotherapy. To test this hypothesis, we evaluated the effect of lovastatin alone, and as an adjuvant chemotherapeutic agent, on th e growth and function of hepatoma tissue culture-4 (HTC-4) cells. Meth ods: HTC-4 cells were treated with lovastatin at concentrations of 1, 3, 5, and 10 mu M, with mitomycin-C at concentrations of 10, 25, 50, a nd 100 nM, or with combinations of the two drugs. Cell growth was eval uated by daily cell counts and substrate adhesion to fibronectin. Resu lts: Lovastatin alone slowed HTC-4 cell growth at concentrations as lo w as 1 mu M (p < 0.01). Mitomycin-C alone slowed HTC-4 cell growth at concentrations of 25 nM and above (p < 0.01). Lovastatin added to mito mycin-C-treated cells resulted in a significant adjuvant effect, with cell growth slowed by an additional 20-30% by 1 mu M lovastatin and by an additional 43-63% by 5 mu M lovastatin, compared to mitomycin-C al one (p < 0.01). Lovastatin-treated cells also exhibited decreased adhe rence to substrate (p < 0.05). Conclusions: Lovastatin is effective al one and as an adjuvant to mitomycin-C in slowing the growth of HTC-4 c ells. These in vitro results support further investigation of lovastat in as an adjuvant chemotherapeutic agent in animal models.