Synergistic anti-tumor effects of liraglutide with metformin on pancreatic cancer cells.
Either metformin or liraglutide has been reported to have anti-tumor effects on pancreatic cancer cells. However, it is not clear whether their combined treatment has additive or synergistic anti-tumor effects on pancreatic cancer cells. In this study, the human pancreatic cancer cell line MiaPaca-2...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2018-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC5999272?pdf=render |
| _version_ | 1818908249887342592 |
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| author | Ran Lu Jin Yang Rui Wei Jing Ke Qing Tian Fei Yu Junling Liu Jingjing Zhang Tianpei Hong |
| author_facet | Ran Lu Jin Yang Rui Wei Jing Ke Qing Tian Fei Yu Junling Liu Jingjing Zhang Tianpei Hong |
| author_sort | Ran Lu |
| collection | DOAJ |
| description | Either metformin or liraglutide has been reported to have anti-tumor effects on pancreatic cancer cells. However, it is not clear whether their combined treatment has additive or synergistic anti-tumor effects on pancreatic cancer cells. In this study, the human pancreatic cancer cell line MiaPaca-2 was incubated with liraglutide and/or metformin. The cell Counting Kit-8 (CCK-8), colony formation, flow cytometry, and wound-healing and transwell migration assays were used to detect cell viability, clonogenic survival, cell cycle and cell migration, respectively. RT-PCR and western blot analyses were used to determine the mRNA and protein levels of related molecules. Results showed that combination treatment with liraglutide (100 nmol/L) and metformin (0.75 mmol/L) significantly decreased cell viability and colony formation, caused cell cycle arrest, upregulated the level of pro-apoptotic proteins Bax and cleaved caspase-3, and inhibited cell migration in the cells, although their single treatment did not exhibit such effects. Combination index value for cell viability indicated a synergistic interaction of liraglutide and metformin. Moreover, the combined treatment with liraglutide and metformin could activate the phosphorylation of AMP-activated protein kinase (AMPK) more potently than their single treatment in the cells. These results suggest that liraglutide in combination with metformin has a synergistic anti-tumor effect on the pancreatic cancer cells, which may be at least partly due to activation of AMPK signaling. Our study provides new insights into the treatment of patients with type 2 diabetes and pancreatic cancer. |
| first_indexed | 2024-12-19T22:08:01Z |
| format | Article |
| id | doaj.art-328133d21b264610ab5563de566d01a4 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-19T22:08:01Z |
| publishDate | 2018-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-328133d21b264610ab5563de566d01a42022-12-21T20:03:58ZengPublic Library of Science (PLoS)PLoS ONE1932-62032018-01-01136e019893810.1371/journal.pone.0198938Synergistic anti-tumor effects of liraglutide with metformin on pancreatic cancer cells.Ran LuJin YangRui WeiJing KeQing TianFei YuJunling LiuJingjing ZhangTianpei HongEither metformin or liraglutide has been reported to have anti-tumor effects on pancreatic cancer cells. However, it is not clear whether their combined treatment has additive or synergistic anti-tumor effects on pancreatic cancer cells. In this study, the human pancreatic cancer cell line MiaPaca-2 was incubated with liraglutide and/or metformin. The cell Counting Kit-8 (CCK-8), colony formation, flow cytometry, and wound-healing and transwell migration assays were used to detect cell viability, clonogenic survival, cell cycle and cell migration, respectively. RT-PCR and western blot analyses were used to determine the mRNA and protein levels of related molecules. Results showed that combination treatment with liraglutide (100 nmol/L) and metformin (0.75 mmol/L) significantly decreased cell viability and colony formation, caused cell cycle arrest, upregulated the level of pro-apoptotic proteins Bax and cleaved caspase-3, and inhibited cell migration in the cells, although their single treatment did not exhibit such effects. Combination index value for cell viability indicated a synergistic interaction of liraglutide and metformin. Moreover, the combined treatment with liraglutide and metformin could activate the phosphorylation of AMP-activated protein kinase (AMPK) more potently than their single treatment in the cells. These results suggest that liraglutide in combination with metformin has a synergistic anti-tumor effect on the pancreatic cancer cells, which may be at least partly due to activation of AMPK signaling. Our study provides new insights into the treatment of patients with type 2 diabetes and pancreatic cancer.http://europepmc.org/articles/PMC5999272?pdf=render |
| spellingShingle | Ran Lu Jin Yang Rui Wei Jing Ke Qing Tian Fei Yu Junling Liu Jingjing Zhang Tianpei Hong Synergistic anti-tumor effects of liraglutide with metformin on pancreatic cancer cells. PLoS ONE |
| title | Synergistic anti-tumor effects of liraglutide with metformin on pancreatic cancer cells. |
| title_full | Synergistic anti-tumor effects of liraglutide with metformin on pancreatic cancer cells. |
| title_fullStr | Synergistic anti-tumor effects of liraglutide with metformin on pancreatic cancer cells. |
| title_full_unstemmed | Synergistic anti-tumor effects of liraglutide with metformin on pancreatic cancer cells. |
| title_short | Synergistic anti-tumor effects of liraglutide with metformin on pancreatic cancer cells. |
| title_sort | synergistic anti tumor effects of liraglutide with metformin on pancreatic cancer cells |
| url | http://europepmc.org/articles/PMC5999272?pdf=render |
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