Investigating the Effect of Ibuprofen on DLL1 and NOTCH1 Expression in Gastric Cancer Stem Cells Derived from MKN-45 Cell Line
<strong>Background:</strong> 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 signalin...
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| Format: | Article |
| Language: | English |
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Shiraz University of Medical Sciences
2019-10-01
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| Series: | Middle East Journal of Cancer |
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| Online Access: | http://mejc.sums.ac.ir/article_45542_91b01dde0c3db6840be07e8de4817854.pdf |
| _version_ | 1818212074408378368 |
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| author | Mohsen Farhangian Frouzan Azarafrouz Hossein Fallahi Hassan Akrami |
| author_facet | Mohsen Farhangian Frouzan Azarafrouz Hossein Fallahi Hassan Akrami |
| author_sort | Mohsen Farhangian |
| collection | DOAJ |
| description | <strong>Background:</strong> 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 1, 2 (COX1,2) activity and synthesis of prostaglandins. Recent studies have provided some evidence for the anti-tumor activities of NSAIDs through inhibition of cell proliferation.<br /> <strong>Methods:</strong> In this study, we investigate the changes in the expression patterns of two key genes, i.e., DLL1 and NOTCH1, which are involved in the Notch signaling pathway in the MKN-45 derived gastric CSCs treated with ibuprofen.<br /> <strong>Results:</strong> Our results showed that ibuprofen up-regulates the expression of the DLL1 gene (4.1 fold) and reduces 68% the transcript level of the NOTCH1 gene (Pvalue < 0.05). These findings show that in gastric CSCs, NOTCH1 gene may act as an oncogene and, conversely, DLL1 gene may act as a tumor suppressor gene.<br /> <strong>Conclusion:</strong> Our findings suggest that ibuprofen, by targeting CSCs, may be used as an adjuvant chemotherapy drug to improve gastric cancer treatment outcomes. |
| first_indexed | 2024-12-12T05:42:37Z |
| format | Article |
| id | doaj.art-783a9d2854b94987bd2921d6431f0816 |
| institution | Directory Open Access Journal |
| issn | 2008-6709 2008-6687 |
| language | English |
| last_indexed | 2024-12-12T05:42:37Z |
| publishDate | 2019-10-01 |
| publisher | Shiraz University of Medical Sciences |
| record_format | Article |
| series | Middle East Journal of Cancer |
| spelling | doaj.art-783a9d2854b94987bd2921d6431f08162022-12-22T00:35:52ZengShiraz University of Medical SciencesMiddle East Journal of Cancer2008-67092008-66872019-10-0110429229810.30476/mejc.2019.78630.45542Investigating the Effect of Ibuprofen on DLL1 and NOTCH1 Expression in Gastric Cancer Stem Cells Derived from MKN-45 Cell LineMohsen Farhangian0Frouzan Azarafrouz1Hossein Fallahi2Hassan Akrami3Department of Biology, Faculty of Sciences, Razi University, Kermanshah, IranDepartment of Biology, Faculty of Sciences, Razi University, Kermanshah, IranDepartment of Biology, Faculty of Sciences, Razi University, Kermanshah, IranDepartment of Biology, Faculty of Sciences, Razi University, Kermanshah, Iran<strong>Background:</strong> 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 1, 2 (COX1,2) activity and synthesis of prostaglandins. Recent studies have provided some evidence for the anti-tumor activities of NSAIDs through inhibition of cell proliferation.<br /> <strong>Methods:</strong> In this study, we investigate the changes in the expression patterns of two key genes, i.e., DLL1 and NOTCH1, which are involved in the Notch signaling pathway in the MKN-45 derived gastric CSCs treated with ibuprofen.<br /> <strong>Results:</strong> Our results showed that ibuprofen up-regulates the expression of the DLL1 gene (4.1 fold) and reduces 68% the transcript level of the NOTCH1 gene (Pvalue < 0.05). These findings show that in gastric CSCs, NOTCH1 gene may act as an oncogene and, conversely, DLL1 gene may act as a tumor suppressor gene.<br /> <strong>Conclusion:</strong> Our findings suggest that ibuprofen, by targeting CSCs, may be used as an adjuvant chemotherapy drug to improve gastric cancer treatment outcomes.http://mejc.sums.ac.ir/article_45542_91b01dde0c3db6840be07e8de4817854.pdfNotch signaling pathwayNonsteroidal anti-inflammatory drugs (NSAIDs)Gastric CancerCancer stem cells (CSCs) |
| spellingShingle | Mohsen Farhangian Frouzan Azarafrouz Hossein Fallahi Hassan Akrami Investigating the Effect of Ibuprofen on DLL1 and NOTCH1 Expression in Gastric Cancer Stem Cells Derived from MKN-45 Cell Line Middle East Journal of Cancer Notch signaling pathway Nonsteroidal anti-inflammatory drugs (NSAIDs) Gastric Cancer Cancer stem cells (CSCs) |
| title | Investigating the Effect of Ibuprofen on DLL1 and NOTCH1 Expression in Gastric Cancer Stem Cells Derived from MKN-45 Cell Line |
| title_full | Investigating the Effect of Ibuprofen on DLL1 and NOTCH1 Expression in Gastric Cancer Stem Cells Derived from MKN-45 Cell Line |
| title_fullStr | Investigating the Effect of Ibuprofen on DLL1 and NOTCH1 Expression in Gastric Cancer Stem Cells Derived from MKN-45 Cell Line |
| title_full_unstemmed | Investigating the Effect of Ibuprofen on DLL1 and NOTCH1 Expression in Gastric Cancer Stem Cells Derived from MKN-45 Cell Line |
| title_short | Investigating the Effect of Ibuprofen on DLL1 and NOTCH1 Expression in Gastric Cancer Stem Cells Derived from MKN-45 Cell Line |
| title_sort | investigating the effect of ibuprofen on dll1 and notch1 expression in gastric cancer stem cells derived from mkn 45 cell line |
| topic | Notch signaling pathway Nonsteroidal anti-inflammatory drugs (NSAIDs) Gastric Cancer Cancer stem cells (CSCs) |
| url | http://mejc.sums.ac.ir/article_45542_91b01dde0c3db6840be07e8de4817854.pdf |
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