Adaptation to statins restricts human tumour growth in Nude mice

Abstract

BackgroundStatins have long been used as anti-hypercholesterolemia drugs, but numerous lines of evidence suggest that they may also bear anti-tumour potential. We have recently demonstrated that it was possible to isolate cancer cells adapted to growth in the continuous presence of lovastatin. These cells grew more slowly than the statin-sensitive cells of origin. In the present study, we compared the ability of both statin-sensitive and statin-resistant cells to give rise to tumours in Nude mice.MethodsHGT-1 human gastric cancer cells and L50 statin-resistant derivatives were injected subcutaneously into Nude mice and tumour growth was recorded. At the end of the experiment, tumours were recovered and marker proteins were analyzed by western blotting, RT-PCR and immunohistochemistry.ResultsL50 tumours grew more slowly, showed a strong decrease in cyclin B1, over-expressed collagen IV, and had reduced laminin 332, VEGF and CD34 levels, which, collectively, may have restricted cell division, cell adhesion and neoangiogenesis.ConclusionsTaken together, these results showed that statin-resistant cells developed into smaller tumours than statin-sensitive cells. This may be reflective of the cancer restricting activity of statins in humans, as suggested from several retrospective studies with subjects undergoing statin therapy for several years.

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“…In addition, lovastatin induced procaspase--7 in a transcriptional manner, as it did for caspase--2 in other digestive cell lines [64], indicating that these caspases could be important drivers of the cytotoxic response elicited in cancer cells. Furthermore, statin--adapted HGT--1 cells grew more slowly in vitro and in vivo when transplanted into immuno--compromised mice, suggesting that adaptation to statins could lower tumor growth in this model [65].…”

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