In Vitro Inhibition of Melanoma (B16f10) Viability and Colonization through Combining Metformin and Dacarbazine
<strong>Background:</strong> Dacarbazine is considered as a standard treatment for melanoma, but resistance to anticancer therapy is a major cause of cancer stem cells invasion. In vitro assays have shown that metformin interferes with cell viability, proliferation, and apoptosis. <st...
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| Format: | Article |
| Language: | English |
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Shiraz University of Medical Sciences
2020-04-01
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| Series: | Middle East Journal of Cancer |
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| Online Access: | http://mejc.sums.ac.ir/article_46415_3e5ceaea0d1b37bed6818af1ac947655.pdf |
| _version_ | 1818645425848057856 |
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| author | Marjan Hajimoradi Javarsiani Shagayegh Haghjooy Javanmard Javad Sajedianfard |
| author_facet | Marjan Hajimoradi Javarsiani Shagayegh Haghjooy Javanmard Javad Sajedianfard |
| author_sort | Marjan Hajimoradi Javarsiani |
| collection | DOAJ |
| description | <strong>Background:</strong> Dacarbazine is considered as a standard treatment for melanoma, but resistance to anticancer therapy is a major cause of cancer stem cells invasion. In vitro assays have shown that metformin interferes with cell viability, proliferation, and apoptosis.
<strong>Method:</strong> Melanoma cell line B16f10 was treated with dacarbazine IC50, metformin in different doses (0.5, 2 and 8 mM) and combination therapy. The influence of treating and cell viability was determined with MTT assay, and the effect of treat on colonization was quantified. Changes in cleaved PARP were investigated using immunoblotting. The cytotoxicity effect of Dacarbazine was further analyzed.
<strong>Result:</strong> Metformin induced cytotoxicity on B16-F10 cells; cell viability, determined at various time intervals (24 and 48 h) and in the presence of different drug concentrations (≅0.7μM), was reduced by ~50% following 24 h. The proliferation rate was evaluated over 24-48 hours and 12 days using varying subcytotoxic and cytotoxic concentrations of metformin (2-8μM), which was reduced in a dose-dependent manner. Resistance cells resulted in slender spindles and better colonization. Finally, metformin decreased the cytotoxicity of dacarbazine and increased apoptosis.
<strong>Conclusion:</strong> A study with B16-F10 cells showed that the drug combination induces significantly more apoptosis compared with when each drug is individually used. B16F10 was the most sensitive and resistant at a normal dose of metformin and dacarbazine, which is a very encouraging result with regards to the possibility of metformin becoming a new tool for melanoma research and treatment. |
| first_indexed | 2024-12-17T00:30:33Z |
| format | Article |
| id | doaj.art-7c0338d40d424b6cb904014f9d037412 |
| institution | Directory Open Access Journal |
| issn | 2008-6709 2008-6687 |
| language | English |
| last_indexed | 2024-12-17T00:30:33Z |
| publishDate | 2020-04-01 |
| publisher | Shiraz University of Medical Sciences |
| record_format | Article |
| series | Middle East Journal of Cancer |
| spelling | doaj.art-7c0338d40d424b6cb904014f9d0374122022-12-21T22:10:20ZengShiraz University of Medical SciencesMiddle East Journal of Cancer2008-67092008-66872020-04-0111215916710.30476/mejc.2019.81250.046415In Vitro Inhibition of Melanoma (B16f10) Viability and Colonization through Combining Metformin and DacarbazineMarjan Hajimoradi Javarsiani0Shagayegh Haghjooy Javanmard1Javad Sajedianfard2Department of Basic Sciences, School of Veterinary Medicine, Shiraz University, Shiraz, IranApplied Physiology Research Center, Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, IranDepartment of Basic Sciences, School of Veterinary Medicine, Shiraz University, Shiraz, Iran<strong>Background:</strong> Dacarbazine is considered as a standard treatment for melanoma, but resistance to anticancer therapy is a major cause of cancer stem cells invasion. In vitro assays have shown that metformin interferes with cell viability, proliferation, and apoptosis. <strong>Method:</strong> Melanoma cell line B16f10 was treated with dacarbazine IC50, metformin in different doses (0.5, 2 and 8 mM) and combination therapy. The influence of treating and cell viability was determined with MTT assay, and the effect of treat on colonization was quantified. Changes in cleaved PARP were investigated using immunoblotting. The cytotoxicity effect of Dacarbazine was further analyzed. <strong>Result:</strong> Metformin induced cytotoxicity on B16-F10 cells; cell viability, determined at various time intervals (24 and 48 h) and in the presence of different drug concentrations (≅0.7μM), was reduced by ~50% following 24 h. The proliferation rate was evaluated over 24-48 hours and 12 days using varying subcytotoxic and cytotoxic concentrations of metformin (2-8μM), which was reduced in a dose-dependent manner. Resistance cells resulted in slender spindles and better colonization. Finally, metformin decreased the cytotoxicity of dacarbazine and increased apoptosis. <strong>Conclusion:</strong> A study with B16-F10 cells showed that the drug combination induces significantly more apoptosis compared with when each drug is individually used. B16F10 was the most sensitive and resistant at a normal dose of metformin and dacarbazine, which is a very encouraging result with regards to the possibility of metformin becoming a new tool for melanoma research and treatment.http://mejc.sums.ac.ir/article_46415_3e5ceaea0d1b37bed6818af1ac947655.pdfmelanomacombination therapymetformincolonization |
| spellingShingle | Marjan Hajimoradi Javarsiani Shagayegh Haghjooy Javanmard Javad Sajedianfard In Vitro Inhibition of Melanoma (B16f10) Viability and Colonization through Combining Metformin and Dacarbazine Middle East Journal of Cancer melanoma combination therapy metformin colonization |
| title | In Vitro Inhibition of Melanoma (B16f10) Viability and Colonization through Combining Metformin and Dacarbazine |
| title_full | In Vitro Inhibition of Melanoma (B16f10) Viability and Colonization through Combining Metformin and Dacarbazine |
| title_fullStr | In Vitro Inhibition of Melanoma (B16f10) Viability and Colonization through Combining Metformin and Dacarbazine |
| title_full_unstemmed | In Vitro Inhibition of Melanoma (B16f10) Viability and Colonization through Combining Metformin and Dacarbazine |
| title_short | In Vitro Inhibition of Melanoma (B16f10) Viability and Colonization through Combining Metformin and Dacarbazine |
| title_sort | in vitro inhibition of melanoma b16f10 viability and colonization through combining metformin and dacarbazine |
| topic | melanoma combination therapy metformin colonization |
| url | http://mejc.sums.ac.ir/article_46415_3e5ceaea0d1b37bed6818af1ac947655.pdf |
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