Title:

Analyzing the role of STAT3 in cisplatin resistant ovarian cancer

In 2018, approximately 22,000 women were diagnosed, and 14,000 women died from ovarian cancer. One reason why this disease is the fifth leading cause of death in women is because it is typically not diagnosed until the disease has progressed to later stages of cancer. Progression of the disease leads to cancerous tumors spreading to other parts of the body (metastasis), and chemotherapy having less of an impact on fighting the cancer (drug resistance) and my research is focused on identifying genes involved in these steps. STAT3 is part of the Signal Transducer and Activator of Transcription (STAT) family and plays a leading role in several cellular functions involved in cellular metastasis, including; cellular proliferation, invasion, migration and angiogenesis. For my thesis work, I focus on genes that are targets of STAT3, such as KLF6, PXN, UGCG and CD44 and how they may be differentially expressed in an ovarian cancer cell line (OVCAR8) that has been adapted to grow either with (Cisplatin Resistant, CR) or without (Cisplatin Sensitive, CS) the presence of chemotherapy. To first confirm these genes to be STAT3 target genes, I used siRNA’s to knockdown the expression of STAT3 target genes in a 3D model to more accurately mimic tumor behavior. Preliminary results of OVCAR8 cells have shown that knocking down STAT3 also results in the reduced expression of KLF6, PXN, UGCG and CD44. Future experiments will include plating CS and CR siRNA treated cells in 3D cultures, treated with either 3uM Cisplatin or media only, and incubated for 7 days. Dyes that label cells for viability (NucBlue) or death (Propidium Iodide) will be added and differences between all treatments visually observed using the EVOS cell imaging system. Cell TiterGlo 3D will subsequently be added and ATP activity (viability of cells) measured and quantified. The overarching goal is to modulate the gene expression of CR cells to make them more sensitive to chemotherapy drugs.

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