Atorvastatin inhibited Rho-associated kinase 1 (ROCK1) and focal adhesion kinase (FAK) mediated adhesion and differentiation of CD133(+)CD44(+) prostate cancer stem cells

作者：Rentala Satyanarayana^*; Chintala Ramakrishna; Guda Manohar; Chintala Madhuri; Komarraju Aruna Lakshmi; Mangamoori Lakshmi Narasu

来源：Biochemical and Biophysical Research Communications, 2013, 441(3): 586-592.

DOI：10.1016/j.bbrc.2013.10.112

• Prostate cancer stem cell
• ROCK1
• FAK
• Integrin
• Differentiation and signaling cascade

Prostate cancer has become a global health concern and is one of the leading causes of cancer death of men after lung and gastric cancers. It has been suggested that the 3-hydroxy-3-methyl-glutarylcoenzyme-CoA (HMG-CoA) reductase inhibitor atorvastatin shows anticancer activity in prostate cancer cell lines. To this end, we analyzed the influence of atorvastatin on the cell adhesion and differentiation of CD1334(+)CD44(+) cells derived from prostate cancer biopsies and peripheral blood. CD133(+)CD44(+) cells were treated with atorvastatin (16-64 mu M) for different time periods. Cell adhesion to endothelial cell monolayers and differentiation into prostate cancer cells were evaluated. alpha 1, beta 1 and alpha 2 beta 1 integrins adhesion receptors and the downstream target of atorvastatin Rho-dependent kinase (ROCK) and focal adhesion kinase (FAR) were analyzed by Western blot. Further blocking studies with the ROCK inhibitor H1152, anti-FAK antibody and anti-integrin alpha 1 and beta 1 antibodies were carried out. Atorvastatin treatment inhibited dose-dependently cell attachment to endothelium and differentiation. The inhibitory effect of atorvastatin on cell adhesion was associated with decreased expression of integrins alpha 1 and beta 1 and phosphorylated MYPT1 and FAK. Furthermore, atorvastatin strongly reduced ROCK1 and FAK mediated differentiation of CD133(+)CD44(+) cells, which was confirmed by antibody treatment. Atorvastatin modified the expression of cell adhesion molecules and differentiation markers. These beneficial effects of atorvastatin may be mediated by ROCK and FAK signaling pathway. The data presented may point to novel treatment options for prostate cancer.

• 出版日期2013-11-22