Investigating the Effect of Ibuprofen on DLL۱ and NOTCH۱ Expression in Gastric Cancer Stem Cells Derived from MKN-۴۵ Cell Line

Background: Cancer stem cells (CSCs) harbor the self-renewal properties of the embryonic stem cells in addition to differentiation. While maintaining the balance between self-renewal and differentiation is required for homeostasis, dysregulation in the stem cell signaling pathways such as Notch signaling increases the proliferation of these cells. As a result, tumorigenic properties are obtained. Therefore, it appears that by targeting the CSCs, the generation of new cells could be reduced and the tumor could be contained. Ibuprofen is one of the nonsteroidal anti-inflammatory drugs that are in use to control pain and inflammation. They inhibit cyclooxygenase ۱, ۲ (COX۱,۲) activity and synthesis of prostaglandins. Recent studies have provided some evidence for the anti-tumor activities of NSAIDs through inhibition of cell proliferation. Methods: In this study, we investigate the changes in the expression patterns of two key genes, i.e., DLL۱ and NOTCH۱, which are involved in the Notch signaling pathway in the MKN-۴۵ derived gastric CSCs treated with ibuprofen. Results: Our results showed that ibuprofen up-regulates the expression of the DLL۱ gene (۴.۱ fold) and reduces ۶۸% the transcript level of the NOTCH۱ gene (Pvalue < ۰.۰۵). These findings show that in gastric CSCs, NOTCH۱ gene may act as an oncogene and, conversely, DLL۱ gene may act as a tumor suppressor gene. Conclusion: Our findings suggest that ibuprofen, by targeting CSCs, may be used as an adjuvant chemotherapy drug to improve gastric cancer treatment outcomes.

کلیدواژه ها:

Notch signaling pathway ، Nonsteroidal anti-inflammatory drugs (NSAIDs) ، Gastric Cancer ، Cancer stem cells (CSCs)