Cho-Chung Y S
Cellular Biochemistry Section, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-1750, USA.
Antisense Nucleic Acid Drug Dev. 1996 Fall;6(3):237-44. doi: 10.1089/oli.1.1996.6.237.
Increased expression of the RI alpha subunit of cAMP-dependent protein kinase type I has been shown in human cancer cell lines, in primary tumors, in cells after transformation, and in cells upon stimulation of growth. The sequence-specific inhibition of RI alpha gene expression by an antisense oligodeoxynucleotide results in the differentiation of leukemia cells and growth arrest of cancer cells of epithelial origin. A single-injection RI alpha antisense treatment in vivo also causes a reduction in RI alpha expression and inhibition of tumor growth. Tumor cells behave like untransformed cells by making less protein kinase type I. The RI alpha antisense, which produces a biochemical imprint for growth control, requires infrequent dosing to restrain neoplastic growth in vivo.
I型环磷酸腺苷依赖性蛋白激酶RIα亚基的表达增加已在人类癌细胞系、原发性肿瘤、转化后的细胞以及生长受刺激的细胞中得到证实。反义寡脱氧核苷酸对RIα基因表达的序列特异性抑制导致白血病细胞分化以及上皮源性癌细胞生长停滞。体内单次注射RIα反义药物也会导致RIα表达降低并抑制肿瘤生长。肿瘤细胞通过减少产生I型蛋白激酶而表现得像未转化细胞。产生生长控制生化印记的RIα反义药物在体内抑制肿瘤生长只需不频繁给药。
