<p>Simvastatin Evokes An Unpredicted Antagonism For Tamoxifen In MCF-7 Breast Cancer Cells</p>

Abstract

PurposeTamoxifen (TAM) is a non-steroidal antiestrogen drug, used in the prevention and treatment of all stages of hormone-responsive breast cancer. Simvastatin (SIM) is a lipid-lowering agent and has been shown to inhibit cancer cell growth. The study aimed to investigate the effect of the combination of TAM and SIM in the treatment of estrogen receptor positive (ER+) breast cancer cell line, MCF-7, and in mice-bearing Ehrlich solid tumors.MethodsMCF-7 cells were treated with different concentrations of TAM or/and SIM for 72 hours and the effects of the combination treatment on cytotoxicity, oxidative stress markers, apoptosis, angiogenesis, and metastasis were investigated using different techniques. In addition, tumor volume, oxidative markers, and inflammatory markers of the combined therapy were explored in mice bearing solid EAC tumors.ResultsThe results showed that treatment of MCF-7 cells with the combination of 10 µM TAM, and 2 µM SIM significantly inhibited the increase in oxidative stress markers, LDH, and NF-kB induced by TAM. In addition, there was a significant decrease in the total apoptotic ratio, caspase-3 activity, and glucose uptake, while there was a non-significant change in Bax/bcl-2 ratio compared to the TAM-treated group. Using the isobologram equation, the drug interaction was antagonistic with combination index, CI=1.18. On the other hand, the combination regimen decreased VEGF, and matrix metalloproteinases, MMP 2&9 compared to TAM-treated cells. Additionally, in vivo, the combination regimen resulted in a non-significant decrease in the tumor volume, decreased oxidative markers, and the protein expression of TNF-α, and NF-κB compared to the TAM treated group.ConclusionAlthough the combination regimen of TAM and SIM showed an antagonistic drug interaction in MCF-7 breast cancer, it displayed favorable antiangiogenic, anti-metastatic, and anti-inflammatory effects.

RETRACTED: The Enhanced Cytotoxic and Pro-Apoptotic Effects of Optimized Simvastatin-Loaded Emulsomes on MCF-7 Breast Cancer Cells

“…The present study clearly shows the enhanced cytotoxic activity exerted by the optimized SMV-EMLs formula on the well-characterized MCF-7 cancer cell model [21,[27][28][29][30][31]53] compared with SMV alone. Despite that, future studies, employing the same experimental conditions, will be carried out in other validated breast cancer cells (e.g., MDA-MB-231) to further validate the relevance of our findings.…”

“…The aim of this work was to investigate the ability of EMLs to improve the cytotoxic and apoptotic efficacy of SMV in human breast cancer (MCF-7) cells. This specific cell line was selected because it represents an established in vitro experimental model in drug discovery processes in the field of oncology to study the toxic potential of SMV alone or in combination with other antineoplastic drugs [ 21 , 27 , 28 , 29 , 30 , 31 ]. A Box–Behnken experimental design was applied to obtain the optimized formula with minimum vesicle size and maximum entrapment efficiency.…”

Simvastatin in the Treatment of Colorectal Cancer: A Review

“…Furthermore, some studies have shown that simvastatin is effective in reducing the risk of colorectal cancer in patients. Many clinical trials have begun to add simvastatin to colorectal cancer chemotherapy regimens for the treatment of patients with metastatic colorectal cancer [14][15][16][17].…”

SIRT1 as a potential key regulator for mediating apoptosis in oropharyngeal cancer using cyclophosphamide and all-trans retinoic acid

“…Primer-set sequences are described in Table 1 . Real-time PCR reactions were performed at 50 °C for 2 min, 95 °C for 10 min, followed by 45 cycles at 95 °C for 15 min and 56 °C for 1 min 28 . The method of Livak and Schmittgen 29 was used to calculate the relative amount of mRNA for the gene.…”