Effect of Pantethine on Ovarian Tumor Progression and Choline Metabolism
Résumé
Epithelial ovarian cancer remains the leading cause of death from ă gynecologic malignancy among women in developed countries. New ă therapeutic strategies evaluated with relevant preclinical models are ă urgently needed to improve survival rates. Here, we have assessed the ă effect of pantethine on tumor growth and metabolism using magnetic ă resonance imaging and high-resolution proton magnetic resonance ă spectroscopy (MRS) in a model of ovarian cancer. To evaluate treatment ă strategies, it is important to use models that closely mimic tumor ă growth in humans. Therefore, we used an orthotopic model of ovarian ă cancer where a piece of tumor tissue, derived from an ovarian tumor ă xenograft, is engrafted directly onto the ovary of female mice, to ă maintain the tumor physiological environment. Treatment with pantethine, ă the precursor of vitamin B5 and active moiety of coenzyme A, was started ă when tumors were similar to 100 mm(3) and consisted of a daily i.p. ă injection of 750 mg/kg in saline. Under these conditions, no side ă effects were observed. High-resolution H-1 MRS was performed on treated ă and control tumor extracts. A dual-phase extraction method based on ă methanol/chloroform/water was used to obtain lipid and water-soluble ă fractions from the tumors. We also investigated effects on metastases ă and ascites formation. Pantethine treatment resulted in slower tumor ă progression, decreased levels of phosphocholine and phosphatidylcholine, ă and reduced metastases and ascites occurrence. In conclusion, pantethine ă represents a novel potential, well-tolerated, therapeutic tool in ă patients with ovarian cancer. Further in vivo preclinical studies are ă needed to confirm the beneficial role of pantethine and to better ă understand its mechanism of action.
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