Identifying the role of Annexin A2 in acquired chemoresistance in triple negative breast cancer (TNBC)

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2021

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Trivedi, Rucha
Vishwanatha, Jamboor

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Abstract

Purpose Triple negative breast cancer accounts for 20% of all breast cancers. Chemotherapy remains the standard of care due to lack of targeted therapy, but patients frequently develop resistance which renders the tumors untreatable. AnnexinA2, a Ca2+-dependent phospholipid binding protein is abundant in TNBC cells. In chemoresistant breast cancer cells, AnnexinA2 is highly overexpressed and shown to reduce sensitivity to chemotherapy drugs by inhibiting apoptosis. Here, we demonstrate the role AnnexinA2 in imparting chemoresistance in TNBC cells. Methods MDA-MB-231 and MCF-7 breast cancer cells were treated with frontline chemotherapy agents to determine the half-maximal inhibitory (IC50) concentration using cell cytotoxicity assay. The cells will be treated with predetermined concentration of drugs and AnnexinA2 protein levels will be analyzed using western blot. AnnexinA2 will be knocked-down or overexpressed to detect the change in sensitivity to the drugs. Results MDA-MB-231 cells were treated with Doxorubicin at concentration of 50 to 10,000 nM for 48 hours and inhibited cell viability in a dose-dependent manner yielding an IC50 of 2,351 nM. AnnexinA2 expression analysis upon Doxorubicin treatment is currently ongoing. AnnexinA2 expression as a function of Doxorubicin, Paclitaxel and Carboplatin exposure to MDA-MB-231 and MCF-7 cells will be presented. Conclusion Preliminary data indicate that Doxorubicin has significant anti-cancer activity on MDA-MB-231 cells with concentrations above 2,000 nM. Future experiments will determine the effect of other chemotherapeutic drugs on TNBC cells and the role of AnnexinA2 in chemoresistance in TNBC.

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