Alpelisib and vorinostat modulate critical genes in basal-2 triple negative breast cancer cells and inhibit cell growth and invasion

Triple negative breast cancer (TNBC) is a heterogeneous disease that continues to be an unmet medicine need. It has a high mortality rate in younger women, especially African Americans. African American women are not sufficiently involved in clinical trials in which novel drugs are being tested. The aggressive and biology of subtypes of this cancer are being researched; however, no targeted therapy has been successful to date. Alpelisib is a selective inhibitor of PIK3 in the PIK3/ATK pathway and has been approved for treatment of advanced metastatic breast cancer. This study was conducted to investigate the effects of Alpelisib and vorinostat (an HDAC inhibitor), either alone or in combination, in the basal-2, a subtype of TNBC, cell line, HCC1806 from a African American woman. Alpelisib alone decreased protein expression of GSKß, crk and DDX5. Alpelisib significantly upregulated the expression of AKT1 protein. In combination with vorinostat, a synergistic effect was noted with AKT1 protein expression. Different isoforms of AKT has been shown to exert anti-cancer effects. Also, the combination significantly decreased GSKß protein expression. GSKß regulates epithelial-mesenchymal transition and cancer stem cell properties. Decreased expression of DDX5 has been shown to result in decreased cell growth. These drugs also decreased invasion. Results from this study suggest that Alpelisib should be further investigated in basal-2 TNBC, alone or in combination with vorinostat.