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Abstract

Cholesterol Homeostasis Modulates Platinum Sensitivity in Human Ovarian Cancer

Ovarian cancer is one of the most severe types of cancers that women can suffer from during their lifetimes. It is the cancer’s tendency for frequent relapses and drug resistance that leads to severity. High grade serous ovarian cancers are characterized by a special oxidative metabolism which has an influence on inflammation and drug resistance. TRAP1 is a chaperone which is involved in the regulation of mitochondrial respiration.

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Platinum is used as an anti-cancer treatment, because it causes apoptosis of cancer cells. In this article, the authors show that platinum-resistant ovarian cancer cells show reduced cholesterol biosynthesis. When they silenced TRAP1, the expression of enzymes which are involved in cholesterol biosynthesis decreased, whereas the expression of LDL (for extracellular cholesterol uptake) increased.

Statins are drugs that inhibit cholesterol synthesis. When the authors treated the cells with statins, they observed a reduced cisplatin-induced apoptosis. Removal of lipids from the culture medium led to a higher drug sensitivity. Thus, the authors highlight the importance of lipid metabolism in ovarian cancer and question the use of statins for treating patients.

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Criscuolo D et al.:
Cholesterol Homeostasis Modulates Platinum Sensitivity in Human Ovarian Cancer