Harada S, Yamamoto N, Fujiki H
Institute for Virus Research, Kyoto-University, Japan.
AIDS Res Hum Retroviruses. 1988 Apr;4(2):99-105. doi: 10.1089/aid.1988.4.99.
We reported previously that TPA facilitates the replication of human immunodeficiency virus (HIV) and has a selective lethal effect on HIV-infected cells by a cytopathic effect induced by HIV. We have now studied the cytopathic effects of TPA-type tumor promoters (teleocidin, aplysiatoxin, and TPA) and the non-TPA type tumor promoters (palytoxin and thapsigargin) on MOLT-4/HIVHTLV-IIIB cells. All TPA-type and non-TPA type tumor promoters tested except palytoxin stimulated in HIV production three- to sevenfold, and caused more lysis of MOLT-4/HIVHTLV-IIIB cells than of the parental MOLT-4 cells. Fifty percent of the MOLT-4/HIVHTLV-IIIB cells were killed by teleocidin, aplysiatoxin, TPA and thapsigargin at concentrations of 2.0, 2.0, 1.0 and 10 ng/ml respectively, and by palytoxin at the very low concentration of 2.0 pg/ml. Moreover, combinations of one TPA-type tumor promoter and one non-TPA type tumor promoter--but not the combination of two TPA-type tumor promoters--had additive lethal effects, supporting the idea that TPA-type and non-TPA type tumor promoters exert their cytolytic effects by different mechanisms. These latter effects may be due to production of prostaglandin E2, which is commonly induced by both types of tumor promoters.
我们先前报道过，佛波酯（TPA）可促进人类免疫缺陷病毒（HIV）的复制，并通过HIV诱导的细胞病变效应对HIV感染细胞产生选择性致死作用。我们现在研究了TPA型肿瘤启动子（远侧素、海兔毒素和TPA）以及非TPA型肿瘤启动子（岩沙海葵毒素和毒胡萝卜素）对MOLT-4/HIVHTLV-IIIB细胞的细胞病变效应。除岩沙海葵毒素外，所有测试的TPA型和非TPA型肿瘤启动子均能使HIV产量提高三至七倍，并且导致MOLT-4/HIVHTLV-IIIB细胞的裂解比亲代MOLT-4细胞更多。远侧素、海兔毒素、TPA和毒胡萝卜素分别在浓度为2.0、2.0、1.0和10 ng/ml时可杀死50%的MOLT-4/HIVHTLV-IIIB细胞，而岩沙海葵毒素在极低浓度2.0 pg/ml时就能达到此效果。此外，一种TPA型肿瘤启动子与一种非TPA型肿瘤启动子的组合——而非两种TPA型肿瘤启动子的组合——具有相加致死效应，这支持了TPA型和非TPA型肿瘤启动子通过不同机制发挥其细胞溶解作用的观点。后一种效应可能是由于前列腺素E2的产生，这两种类型的肿瘤启动子通常都会诱导其产生。
