Tamoxifen Downregulates the Expression of Notch1 and DLL1 Genes in MKN-45 Gastric Cancer Cells
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ORIGINAL RESEARCH
Tamoxifen Downregulates the Expression of Notch1 and DLL1 Genes in MKN-45 Gastric Cancer Cells Faranak Khanipouyani 1 & Hassan Akrami 2
# Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Purpose Gastric cancer is one of the most prevalent cancers worldwide and the second most common cause for cancer associated mortality. Anti-tumor effects of tamoxifen in breast cancer are well-established. However, no study has so far investigated the effects of tamoxifen on gene expression of Notch1 and DLL1 in gastric cancer cell line. The present study was conducted to explore the effects of tamoxifen, as a repurposed drug, on gene expression of Notch1 and DLL1 in MKN-45, a gastric cancer cell line. Methods MKN-45 cells were cultured in DMEM/F12 medium containing 10% FBS. Cytotoxic effects of tamoxifen on these cells at various concentrations were evaluated by trypan blue exclusion assay. For gene expression analysis, the cells were first incubated with 100 μM tamoxifen followed by total RNA extraction from treated and control cells. Then, cDNA was synthesized. Quantitative real-time PCR using specific primers for Notch1 and DLL1 was performed to assess the effect of tamoxifen on the transcript of them. Results Treatment with tamoxifen decreased viability of MKN-45 cells in a dose-dependent manner. CC50 was estimated to be around 200 μM. Also, tamoxifen at the dose of 100 μM could significantly downregulate mRNA levels of both Notch1 and DLL1 genes as compared with untreated cells by 24% and 92%, respectively. Conclusion Based on these results, tamoxifen interferes with Notch signaling pathway through downregulating the expression of Notch1 and DLL1 genes and this could be regarded as a mechanism for its anti-cancer effects in this malignant disease. Key words Gastric cancer . MKN-45 . Tamoxifen . Notch1 . DLL1 . Repurposed drug
Abbreviations DLL1 Delta like canonical Notch ligand 1 DMEM Dulbecco’s modified Eagle’s medium FBS Fetal bovine serum cDNA Complementary DNA PCR Polymerase chain reaction CC50 50% cytotoxic concentration
* Hassan Akrami [email protected]; [email protected] 1
Department of Biology, Faculty of Science, Razi University, Kermanshah, Iran
2
Gastroenterohepatology Research Center, Shiraz University of Medical Sciences, Shiraz 71935-1311, Iran
Introduction Drug repositioning (or drug repurposing) is defined as finding novel medical applications for the existing drugs which can be viewed as a new approach of discovering novel therapeutic/ preventive indications for the previously approved medications with low cost, good safety, and high efficiency. Drug repositioning can precipitate drug entry to the clinic as pharmacological and toxicological data of the drug have been previously determined [1]. Gastric cancer (GC) is one of the most prevalent cancers and the second most usual cause for cancer-related death, worldwide. Various studies have shown that the rate of GC incidence is strongly increasing among the youth [2, 3]. Despite prolific studies on
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