Abstract
Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer that disproportionately affects women under the age of 40, as well as minority women. TNBC lacks the three main receptors for cancer therapies: estrogen receptors, progesterone receptors, and human epidermal growth factor receptor 2 (HER2), which serve as targets for treatment. Because of this, treatment relies heavily on surgery and chemotherapy, and is often unsuccessful, as TNBC is highly metastatic and known to develop drug resistance. As a result, novel anti-cancer and anti-metastatic therapies are needed for the treatment of TNBC. Recently, the stilbene compound, resveratrol, has gained popularity in breast cancer research for its anti-cancer properties. In this thesis, resveratrol and four analogue compounds were analyzed for anti-metastatic capabilities towards TNBC through in vitro experiments to assess cell migration and invasion, as well as tumor formation and integrity through the development of a multicellular tumor spheroid (MTS) model. Results showed that these stilbene compounds have significant effects on cell migration, and for some, cell invasion. The MTS model showed that a novel stilbene compound, analogue 4c, dramatically changes MTS morphology and size, as well as the ability of cells to form an MTS. 4c was analyzed through qPCR gene expression assays to assess the mechanism behind the anti-metastatic effects on TNBC cell lines. Results show a trend of down-regulated mesenchymal protein markers suggesting that reversal of the epithelial-to-mesenchymal transition is responsible for the changes observed. Results also show that 4c interferes with cell migration, and tumor growth and formation, a promising result for metastatic tumor treatment. Cell migration and tumor formation relate to key steps in the metastatic pathway, therefore, the ability of analogue 4c to reduce both suggests that the drug has the potential to inhibit metastatic disease of TNBC, which is primarily responsible for patient mortality.
