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Georgia Journal of Science

Article Title

THE ROLE OF LEPTIN IN TRIPLE NEGATIVE BREAST CANCER TREATED WITH CHEMOTHERAPEUTICS

Abstract

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. Hypothesis: Leptin is a proliferative and survival factor for TNBC that could reduce the effectiveness of commonly used drugs: Doxorubicin (DOX) and 5-fluorouracil (5-FU). Methods: TNBC cell lines MDA-MB-231 and MDA-MB 468 were seeded (2x105 cells) in six well plates. Cells were cultured and at 80% confluent 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; 8) 2.5nM leptin, 2.5nM PEG-LPrA2 plus 5-FU ED50, apoptosis and cell cycle were determined after treatment. All treatments lasted 6 days. Nexcelom Cellometer technology was used to complete Annexin V assay for apoptosis and PI staining for cell cycle assay. Results: 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. Discussion: 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.

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