Tamoxifen Downregulates the Expression of Notch1 and DLL1 Genes in MKN-45 Gastric Cancer Cells.

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. CC 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.