Statins and LXR receptor agonists offer ovarian cancer hope
MedWire News: Statins and liver X receptor (LXR) agonists could become an effective adjunct therapy against ovarian cancer, US researchers say.
The Los Angeles team found that fluvastatin and the synthetic LXR agonist TO901317 reversed the impact of oxidized low-density lipoprotein (LDL) in reducing carcinoma cell chemosensitivity and stimulating proliferation.
Daniel Scoles, from Cedars-Sinai Medical Center, and colleagues say: “Our data suggest further investigation into the use of statins and LXR agonists as adjunctive therapies for ovarian cancer is merited.”
The study revealed that concentrations of oxLDL as low as 0.1 µg/ml stimulated the proliferation of the ovarian carcinoma cell lines CAOV3 and SKOV3, which possess the Cluster of Differentiation (CD)36 scavenger receptor. LDL, in contrast, had no such effect.
TO901317 inhibited the proliferation of CAOV3, OVCAR3, and SKOV3 cell lines stimulated by oxLDL, while fluvastatin inhibited oxLDL-mediated proliferation of the CAOV3 and SKOV3 cell lines.
The anti-apoptotic cytokine cardiotrophin 1 was mitogenic to the CAOV3 and SKOV3 cell lines, and was induced by oxLDL but reversed by TO901317.
The observation that oxLDL potently stimulated the proliferation of ovarian cancer cells led the researchers to question whether oxLDL could alter the sensitivity of ovarian cancer cells to chemotherapy.
Further analysis showed that treating both CAOV3 and SKOV3 cells with oxLDL increased cisplatin IC50s, the concentration of the chemotherapy drug required for 50% inhibition of its target.
Comparison of several ovarian carcinoma cell lines led the researchers to conclude that LXR pathway proteins are expressed in most of these cell lines.
Reporting in the journal Gynecologic Oncology, they write: “Our study demonstrated that increases in oxidized LDL cholesterol may negatively impact ovarian cancer outcome and suggests that LXR ligands and statins may be an effective strategy for treating ovarian cancer patients.”
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By Anita Wilkinson