کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
3164153 1198770 2013 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Atorvastatin inhibits RhoC function and limits head and neck cancer metastasis
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی دندانپزشکی، جراحی دهان و پزشکی
پیش نمایش صفحه اول مقاله
Atorvastatin inhibits RhoC function and limits head and neck cancer metastasis
چکیده انگلیسی

SummaryObjectiveRhoC oncogene is a well characterized marker of metastasis in a majority of invasive cancers, including HNSCC. Elevated RhoC expression has been found to be associated with distant metastasis. Statins are a class of drugs that are used to reduce cholesterol levels by inhibiting HMG-CoA reductase activity which in turns prevents mevalonate synthesis, which is a precursor for synthesis of cholesterol and prenylation. Interestingly, the proper function of Rho proteins depends on prenylation. Significantly, it has been reported that metastasis in human melanoma can be reduced by atorvastatin which inhibits RhoC activity by preventing its geranylgeranylation. Given that RhoC is a key oncogene involved in metastasis, we hypothesized Atorvastatin can reduce head and neck metastasis by inhibiting RhoC activity.MethodsIn vitro and in vivo studies were carried out to evaluate the ability of Atorvastatin to inhibit RhoC function and HNSCC metastasis. Cell motility, proliferation, cell invasion, and colony formation assays were performed according to the standard protocols.ResultsAtorvastatin treatment significantly reduced the active form of RhoC in vitro and diminished cell motility, invasion, proliferation and colony formation. Importantly, we observed a significant decrease in p-ERK1/2 and p-STAT3 in Atorvastatin treated cell lines. In vivo experiments revealed inhibition of angiogenesis and lung metastases with Atorvastatin therapy.ConclusionsThis study is the first of its kind to establish a potential role of Atorvastatin in head and neck cancer therapy. These findings suggest that Atorvastatin can be a potential low risk adjuvant therapy to minimize metastases in aggressive forms of HNSCC.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Oral Oncology - Volume 49, Issue 8, August 2013, Pages 778–786
نویسندگان
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