Chapekar M S, Knode M C, Glazer R I
Laboratory of Biological Chemistry, National Cancer Institute, Bethesda, Maryland 20892.
Mol Pharmacol. 1988 Oct;34(4):461-6.
The human epidermoid carcinoma cell line A431, containing an amplification in the epidermal growth factor (EGF) receptor gene, was examined for its sensitivity to the growth inhibitory effects of synthetic double-stranded RNAs (dsRNAs). Poly(I).poly(C), poly(A).poly(U) and rln.r(C13,U)n at 5 to 100 micrograms/ml produced 20 to 60% growth inhibition, whereas poly(ICLC) produced 40 to 80% growth inhibition at 0.05 to 25 micrograms/ml.Poly(I).poly(C) did not cause the secretion of interferon (IFN) into the medium, and addition of polyclonal antibodies to IFN-alpha and IFN-beta did not block the growth inhibition produced by poly(I).poly(C). Clone 29, which proliferates in response to EGF, and clone 29R, which is sensitive to the growth inhibitory effects of EGF, showed sensitivities to the antiproliferative effects of poly(I).poly(C) similar to those of the parent cell line. Incubation of cell membrane extracts with poly(I).poly(C) or treatment of cells with the dsRNA did not affect EGF receptor tyrosine kinase activity. On the other hand, poly(I).poly(C) produced a dose-dependent induction of (2',5')oligo(A) synthetase activity and degradation of 45S preribosomal RNA and 28S and 18S rRNA. These results indicate that the growth inhibitory properties of poly(I).poly(C) in A431 cells are independent of the action of IFN but are associated with degradation of rRNA, an effect that may be related to the (2',5')oligo(A)-RNase L pathway.
人表皮样癌细胞系A431含有表皮生长因子（EGF）受体基因扩增，对其进行了合成双链RNA（dsRNA）生长抑制作用的敏感性检测。5至100微克/毫升的聚肌苷酸-聚胞苷酸[Poly(I).poly(C)]、聚腺苷酸-聚尿苷酸[poly(A).poly(U)]和rln.r(C13,U)n产生20%至60%的生长抑制，而聚肌胞苷酸（聚肌苷酸-聚胞苷酸）[poly(ICLC)]在0.05至25微克/毫升时产生40%至80%的生长抑制。聚肌苷酸-聚胞苷酸不会导致干扰素（IFN）分泌到培养基中，添加针对IFN-α和IFN-β的多克隆抗体不会阻断聚肌苷酸-聚胞苷酸产生的生长抑制。对EGF有增殖反应的克隆29和对EGF生长抑制作用敏感的克隆29R，对聚肌苷酸-聚胞苷酸抗增殖作用的敏感性与亲代细胞系相似。用聚肌苷酸-聚胞苷酸孵育细胞膜提取物或用dsRNA处理细胞不会影响EGF受体酪氨酸激酶活性。另一方面，聚肌苷酸-聚胞苷酸产生剂量依赖性的(2',5')寡聚腺苷酸合成酶活性诱导以及45S前核糖体RNA和28S及18S rRNA的降解。这些结果表明，聚肌苷酸-聚胞苷酸在A431细胞中的生长抑制特性与IFN的作用无关，但与rRNA降解有关，这种作用可能与(2',5')寡聚腺苷酸-RNase L途径有关。
