Shen, Ming ORCID: https://orcid.org/0000-0002-3891-7231, Samsel, Paulina, Shen, Louise L., Narov, Kalin, Yang, Jian ORCID: https://orcid.org/0000-0003-2631-4553 and Sampson, Julian ORCID: https://orcid.org/0000-0002-2902-2348 2017. Assessment of response of kidney tumours to rapamycin and atorvastatin in Tsc1+/- mice. Translational Oncology 10 (5) , pp. 793-799. 10.1016/j.tranon.2017.07.009 |
Preview |
PDF
- Published Version
Available under License Creative Commons Attribution Non-commercial No Derivatives. Download (2MB) | Preview |
Abstract
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 ofmouse Tsc2 null embryonic fibroblasts through inhibition ofmTOR. 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-weightedmagnetic resonance imaging to track changes in tumor number and size in the kidneys of a Tsc1+/− mousemodel 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.
Item Type: | Article |
---|---|
Date Type: | Publication |
Status: | Published |
Schools: | Medicine |
Subjects: | R Medicine > R Medicine (General) |
Publisher: | Elsevier |
ISSN: | 1944-7124 |
Funders: | TSA and Wales Gene Park |
Date of First Compliant Deposit: | 3 August 2017 |
Date of Acceptance: | 31 July 2017 |
Last Modified: | 19 Feb 2024 06:23 |
URI: | https://orca.cardiff.ac.uk/id/eprint/103290 |
Citation Data
Cited 2 times in Scopus. View in Scopus. Powered By Scopus® Data
Actions (repository staff only)
Edit Item |