Tamoxifen synergizes the antiproliferative effect of cisplatin in human ovarian cancer cells: enhancement of DNA platination as a possible mechanism

Cancer Letters
A ErcoliS Mancuso

Abstract

We investigated the chemosensitizing activity of tamoxifen (TAM) on estrogen receptor negative ovarian cancer cell lines sensitive (A2780 WT) and resistant to cisplatin (CP) (A2780 CP3). Our results showed that the treatment of both cell lines with the association TAM + CP (concentration range 0.01-1 microN and 0.1-1 microgram/ml, respectively) results in a synergistic antiproliferative activity and a complete reversal of the acquired CP-resistant phenotype. We demonstrated that in A2780 cells the addition of TAM to CP treatment is able to significantly enhance at every tested CP dose (P < 0.001) the amount of platinum (Pt) bound to the DNA. Since Pt-DNA levels in the genome are clearly related to the growth inhibitory effect of CP (correlation value = 0.97, P < 0.001) in our experimental model, we hypothesized that TAM could act synergistically with CP and overcome the acquired CP-resistance by enhancing Pt binding to the DNA. We suggest that, from a clinical point of view, TAM may be usefully included in CP-based chemotherapy regimens for ovarian cancer patients since plasma concentrations of the drug capable of in vitro CP resistance modulation are achievable in vivo. A prospective clinical trial to verify the clinical usefu...Continue Reading

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Citations

Aug 12, 1998·Obstetrics and Gynecology·A K Sood, R E Buller
Mar 18, 1999·Hematology/oncology Clinics of North America·G Emons, J J Kavanagh
Apr 12, 2014·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·You ZhouZhi-Qiang Ning
Mar 22, 2002·International Journal of Gynecological Cancer : Official Journal of the International Gynecological Cancer Society·P Benedetti PaniciS Mancuso
Sep 23, 2008·Expert Opinion on Pharmacotherapy·Peng H Tan, Amrit S Lota
Feb 24, 2000·Gynecological Endocrinology : the Official Journal of the International Society of Gynecological Endocrinology·A Gadducci, A R Genazzani
Aug 16, 2017·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Max KatesTrinity J Bivalacqua

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