Statins may inhibit metastases, according to research using high-throughput drug screens. Fluvastatin was identified as one promising inhibitor, atorvastatin and simvastatin as well as others also showed positive results.
The scientists presented their findings in the journal Clinical and Translational Medicine.
More than ten years ago, Professor Ulrike Stein and her lab at the Experimental and Clinical Research Center (ECRC) uncovered an important driver of metastasis in human colorectal cancer—the metastasis-associated in colon cancer 1 (MACC1) gene. MACC1 is now a known prognostic and predictive biomarker for more than 20 solid tumor entities
When cancer cells express MACC1, their ability to proliferate, move around the body, and invade other tissues is enhanced, according to Stein’s lab’s work.
“Many types of cancers spread only in patients with high MACC1 expression,” Stein explains. MACC1’s role as a key factor and biomarker of tumor growth and metastasis—not only in colorectal cancer, but in solid tumors such as gastric, liver and breast cancer—has since been studied by many other researchers worldwide and confirmed in more than 300 publications.
Now, together with Robert Preissner of Charité, Universitätsmedizin Berlin, Stein has shown that statins, which are prescribed as cholesterol-lowering drugs, inhibit MACC1 expression in tumor cells.
In their search for MACC1 inhibitors, the researchers conducted high-throughput drug screening with colleagues at the European Molecular Biology Laboratory (EMBL) in Heidelberg, Germany. The teams independently hit upon statins. Fluvastatin. Atorvastatin, and simvastatin were among the drugs that reduced MACC1 mRNA and protein expression in a concentration-dependent manner.
They tested this discovery on various tumor cell lines, including pancreatic and gastric cancer cells, with favorable results. Seven drugs tested reduced MACC1 expression in the cells but to varying degrees. The scientists then administered the cholesterol inhibitors to genetically modified mice with increased MACC1 expression. This almost completely suppressed the formation of tumors and metastases in the animals. “What is particularly remarkable is that the benefits continued in the animals even after we reduced the dose relative to the amount that humans normally ingest,” Stein says.
The researchers write “At a molecular/mechanistic level, we provide experimental evidence that statins act, at least partly, by inhibiting transcription of the tumor-promoting and metastasis-inducing MACC1 gene.”
Preissner, a senior author on the paper, and scientists at the University of Virginia also examined data from a total of 300,000 patients who had been prescribed statins. This analysis found a correlation. “Patients taking statins had only half the incidence of cancer compared to the general population,” Preissner said.
Stein advises against taking statins as a preventive measure without consulting a doctor and having lipid levels checked, so as to ensure no serious side effects occur.
“We are still at the very beginning,” the scientist stresses. “Cell lines and mice are not human beings, so we cannot directly transfer the results.” The experimental studies and retrospective data analysis will now be followed up by a clinical trial, she says. Only after that will it be possible to say with certainty whether statins actually prevent or reduce metastasis in patients with high MACC1 expression.
