Pal Ajai, Ahmad Ateeq, Khan Sumsullah, Sakabe Isamu, Zhang Chuanbo, Kasid Usha N, Ahmad Imran
Pharmacokinetics, Safety and Efficacy Department, NeoPharm Inc., Research and Development, 1850 Lakeside Drive, Waukegan, IL 60085, USA.
Int J Oncol. 2005 Apr;26(4):1087-91.
Raf-1, a protein serine-threonine kinase, plays a critical role in mitogen-activated protein kinase kinase (MKK/MEK)- mitogen-activated protein kinase (extracellular signal-regulated kinase) (MAPK/ERK) pathways. We show here that systemically delivered novel cationic cardiolipin liposomes (NeoPhectin-AT) containing a small interfering RNA (siRNA) against Raf-1 silence the expression of Raf-1 in tumor tissues and inhibit tumor growth in xenograft model of human prostate cancer. The knockdown of Raf-1 expression by siRNA is also associated with down-regulation of cyclin D1 expression in vivo.
Raf-1是一种蛋白质丝氨酸-苏氨酸激酶,在丝裂原活化蛋白激酶激酶(MKK/MEK)-丝裂原活化蛋白激酶(细胞外信号调节激酶)(MAPK/ERK)信号通路中起关键作用。我们在此表明,系统性递送的含有针对Raf-1的小干扰RNA(siRNA)的新型阳离子心磷脂脂质体(NeoPhectin-AT)可使肿瘤组织中Raf-1的表达沉默,并在人前列腺癌异种移植模型中抑制肿瘤生长。siRNA对Raf-1表达的敲低在体内还与细胞周期蛋白D1表达的下调相关。