THE ROLE OF LEPTIN IN TRIPLE NEGATIVE BREAST CANCER TREATED WITH CHEMOTHERAPEUTICS
Triple negative breast cancer (TNBC) tumors lack estrogen, progesterone and HER2 receptor expression, and its occurrence has been linked to obesity. Chemotherapy remains as the key therapy for TNBC, as there is no targeted treatment. Leptin is a hormone secreted mainly by the adipose tissue that is elevated in obese people. Leptin signaling could affect TNBC survival during chemotherapy, which may open a new ways to combat the disease and reduce chemoresistance. We hypothesize that Leptin is a proliferative and survival factor for TNBC that could reduce the effectiveness of the commonly used drugs Doxorubicin (DOX) and 5-fluorouracil (5-FU). TNBC cell lines MDA-MB-231 and MDA-MB 468 were treated, as follows: 1) basal medium; 2) 2.5nM leptin; 3) 2.5nM leptin plus 2.5nM PEG-LPrA2 (pegylated leptin antagonist developed by us); 4) DOX at ED50 5) 5-FU at ED50; 5) 2.5nM leptin plus DOX; 6) leptin plus 5-FU; 7) 2.5nM leptin, 2.5nM PEG-LPrA2 plus DOX ED50; or 8) 2.5nM leptin, 2.5nM PEG-LPrA2 plus 5-FU ED50. Apoptosis and cell cycle progression were determined after 6 day treatments using Nexcelom Cellometer technology to complete Annexin V assays for apoptosis and PI staining for cell cycle assays. Results indicate that leptin increased cell cycle progression by inducing progression of S phase. DOX and 5-FU induced apoptosis, which was attenuated by leptin. PEG-LPrA2 abrogated leptin effects on cell cycle and survival with chemotherapeutics. These data indicate that high levels of leptin in obese TNBC patient can decrease chemotherapeutic effectiveness and induce drug resistance. Thus, inhibiting leptin signaling using antagonist could serve as a new strategy to improve chemotherapeutic effectiveness, decrease drug resistance and reduce dosage of chemotherapeutics.
Kurian, Ann A. and Gonzalez-Perez, Ruben Rene
"THE ROLE OF LEPTIN IN TRIPLE NEGATIVE BREAST CANCER TREATED WITH CHEMOTHERAPEUTICS,"
Georgia Journal of Science, Vol. 75, No. 1, Article 33.
Available at: http://digitalcommons.gaacademy.org/gjs/vol75/iss1/33
This document is currently not available here.