Assessment of Response of Kidney Tumors to Rapamycin and Atorvastatin in Tsc1+/− Mice
Atorvastatin is widely used to lower blood cholesterol and to reduce risk of cardiovascular disease–associated complications. Epidemiological investigations and preclinical studies suggest that statins such as atorvastatin have antitumor activity for various types of cancer. Tuberous sclerosis (TSC)...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2017-10-01
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| Series: | Translational Oncology |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1936523317300761 |
| _version_ | 1818479761866883072 |
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| author | Ming Hong Shen Paulina Samsel Louise L. Shen Kalin Narov Jian Yang Julian R. Sampson |
| author_facet | Ming Hong Shen Paulina Samsel Louise L. Shen Kalin Narov Jian Yang Julian R. Sampson |
| author_sort | Ming Hong Shen |
| collection | DOAJ |
| description | Atorvastatin is widely used to lower blood cholesterol and to reduce risk of cardiovascular disease–associated complications. Epidemiological investigations and preclinical studies suggest that statins such as atorvastatin have antitumor activity for various types of cancer. Tuberous sclerosis (TSC) is a tumor syndrome caused by TSC1 or TSC2 mutations that lead to aberrant activation of mTOR and tumor formation in multiple organs. Previous studies have demonstrated that atorvastatin selectively suppressed growth and proliferation of mouse Tsc2 null embryonic fibroblasts through inhibition of mTOR. However, atorvastatin alone did not reduce tumor burden in the liver and kidneys of Tsc2+/− mice as assessed by histological analysis, and no combination therapy of rapamycin and atorvastatin has been tried. In this study, we used T2-weighted magnetic resonance imaging to track changes in tumor number and size in the kidneys of a Tsc1+/− mouse model and to assess the efficacy of rapamycin and atorvastatin alone and as a combination therapy. We found that rapamycin alone or rapamycin combined with atorvastatin significantly reduced tumor burden, while atorvastatin alone did not. Combined therapy with rapamycin and atorvastatin appeared to be more effective for treating renal tumors than rapamycin alone, but the difference was not statistically significant. We conclude that combined therapy with rapamycin and atorvastatin is unlikely to provide additional benefit over rapamycin as a single agent in the treatment of Tsc-associated renal tumors. |
| first_indexed | 2024-12-10T11:15:01Z |
| format | Article |
| id | doaj.art-d46705bbfdce49699e9d8199866c06ff |
| institution | Directory Open Access Journal |
| issn | 1936-5233 1944-7124 |
| language | English |
| last_indexed | 2024-12-10T11:15:01Z |
| publishDate | 2017-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Translational Oncology |
| spelling | doaj.art-d46705bbfdce49699e9d8199866c06ff2022-12-22T01:51:14ZengElsevierTranslational Oncology1936-52331944-71242017-10-0110579379910.1016/j.tranon.2017.07.009Assessment of Response of Kidney Tumors to Rapamycin and Atorvastatin in Tsc1+/− MiceMing Hong Shen0Paulina Samsel1Louise L. Shen2Kalin Narov3Jian Yang4Julian R. Sampson5Institute of Medical Genetics, Division of Cancer and Genetics, School of Medicine, Cardiff University, Heath Park, Cardiff CF14 4XN, UKInstitute of Medical Genetics, Division of Cancer and Genetics, School of Medicine, Cardiff University, Heath Park, Cardiff CF14 4XN, UKJohn Radcliffe Hospital, Headley Way, Headington, Oxford, Oxfordshire, OX3 9DUInstitute of Medical Genetics, Division of Cancer and Genetics, School of Medicine, Cardiff University, Heath Park, Cardiff CF14 4XN, UKInstitute of Medical Genetics, Division of Cancer and Genetics, School of Medicine, Cardiff University, Heath Park, Cardiff CF14 4XN, UKInstitute of Medical Genetics, Division of Cancer and Genetics, School of Medicine, Cardiff University, Heath Park, Cardiff CF14 4XN, UKAtorvastatin is widely used to lower blood cholesterol and to reduce risk of cardiovascular disease–associated complications. Epidemiological investigations and preclinical studies suggest that statins such as atorvastatin have antitumor activity for various types of cancer. Tuberous sclerosis (TSC) is a tumor syndrome caused by TSC1 or TSC2 mutations that lead to aberrant activation of mTOR and tumor formation in multiple organs. Previous studies have demonstrated that atorvastatin selectively suppressed growth and proliferation of mouse Tsc2 null embryonic fibroblasts through inhibition of mTOR. However, atorvastatin alone did not reduce tumor burden in the liver and kidneys of Tsc2+/− mice as assessed by histological analysis, and no combination therapy of rapamycin and atorvastatin has been tried. In this study, we used T2-weighted magnetic resonance imaging to track changes in tumor number and size in the kidneys of a Tsc1+/− mouse model and to assess the efficacy of rapamycin and atorvastatin alone and as a combination therapy. We found that rapamycin alone or rapamycin combined with atorvastatin significantly reduced tumor burden, while atorvastatin alone did not. Combined therapy with rapamycin and atorvastatin appeared to be more effective for treating renal tumors than rapamycin alone, but the difference was not statistically significant. We conclude that combined therapy with rapamycin and atorvastatin is unlikely to provide additional benefit over rapamycin as a single agent in the treatment of Tsc-associated renal tumors.http://www.sciencedirect.com/science/article/pii/S1936523317300761 |
| spellingShingle | Ming Hong Shen Paulina Samsel Louise L. Shen Kalin Narov Jian Yang Julian R. Sampson Assessment of Response of Kidney Tumors to Rapamycin and Atorvastatin in Tsc1+/− Mice Translational Oncology |
| title | Assessment of Response of Kidney Tumors to Rapamycin and Atorvastatin in Tsc1+/− Mice |
| title_full | Assessment of Response of Kidney Tumors to Rapamycin and Atorvastatin in Tsc1+/− Mice |
| title_fullStr | Assessment of Response of Kidney Tumors to Rapamycin and Atorvastatin in Tsc1+/− Mice |
| title_full_unstemmed | Assessment of Response of Kidney Tumors to Rapamycin and Atorvastatin in Tsc1+/− Mice |
| title_short | Assessment of Response of Kidney Tumors to Rapamycin and Atorvastatin in Tsc1+/− Mice |
| title_sort | assessment of response of kidney tumors to rapamycin and atorvastatin in tsc1 mice |
| url | http://www.sciencedirect.com/science/article/pii/S1936523317300761 |
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