RESUMO
BACKGROUND: Cancer drug resistance poses a significant risk of relapse and mortality. Adjuvant tamoxifen use has significantly reduced breast cancer mortality; however, many patients relapse due to acquired resistance. We aim to assess the potential of a cholesterol depletor (acetyl plumbagin) combined with tamoxifen to reduce cholesterol accumulation and cancer drug resistance. MATERIALS AND METHODS: Cell viability, apoptosis and cholesterol staining was assessed following combination treatment. Gene and protein expression in cancer drug resistance and lipoprotein signalling pathways were assessed using RT2 Profiler™ PCR arrays and STRING networks. RESULTS: Combined treatment led to an increase in apoptosis and reduced intracellular cholesterol in MCF-7 and long-term estrogen deprived (LTED) cells compared to single compound treatments. Furthermore, the combination treatment perturbed several cholesterol-related and cancer-drug resistance pathways. CONCLUSION: The present study demonstrates the efficacy of tamoxifen combined with acetyl plumbagin in potentially disrupting the PI3K/Akt/PKB and Akt/mTORC1 signalling pathways in MCF-7 cells, reducing breast cancer cell proliferation and resistance.
