Prevention of neocarzinostatin-induced cell death and morphologic change in SK-N-SH human neuroblastoma cells by continuous exposure to nerve growth factor.
Prevention of neocarzinostatin-induced cell death and morphologic change in SK-N-SH human neuroblastoma cells by continuous exposure to nerve growth factor.
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通过持续暴露于神经生长因子来预防新制癌菌素诱导的 SK-N-SH 人神经母细胞瘤细胞的细胞死亡和形态变化。
DOI：
10.1016/0006-2952(93)90561-a
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发表时间：
1993
影响因子：
5.8
通讯作者：
Schor,NF
中科院分区：
文献类型：
--
作者：
Falcione,M;Milligan,KD;Schwartz,MC;Schor,NF
新卡西宁是一种抗肿瘤药物，可在体外诱导人(SK-N-SH)神经母细胞瘤细胞分化。我们将这种形态分化与内源性分化诱导剂神经生长因子(NGF)诱导的形态分化进行了比较，并探讨了NGF对新卡西汀诱导的SK-N-SH细胞形态变化的影响。NGF和新卡宾抑素均可诱导这些细胞突起生长。然而，在NGF存在下形成的这些过程比新卡西诺他汀诱导的过程更短和更细。此外，只有新卡西诺他汀才能诱导细胞的体细胞增大，并在培养的浓度依赖的部分导致细胞死亡。这些处理细胞的明显特征使我们能够确定NGF暴露是否改变了细胞对新卡西诺他汀的反应。神经生长因子可保护SK-N-SH细胞免受新卡西诺他汀(0.017~0.033μg/mL，1小时)的形态和细胞毒作用。对新卡西诺他汀的保护要求NGF在暴露新卡西诺他汀前24小时持续存在一段时间，并在实验期间持续存在，这意味着NGF提供的保护具有需要预先处理的潜伏期，并且是可逆的。这些结果表明，新卡西诺抑素被细胞摄取，并在NGF被移除后发挥作用，即使在新卡西诺他汀被冲出培养基后也是如此。NGF受体结合所触发的信号转导通路可能阻止新卡西诺抑素的作用或抑制新卡西诺他汀诱导的SK-N-SH细胞表达变化。
Neocarzinostatin is an antineoplastic agent that induces differentiated morphology in human (SK-N-SH) neuroblastoma cells in culture. We have compared this morphological differentiation with that induced by the endogenous differentiation inducer, nerve growth factor (NGF), and have explored the effects of exposure to NGF upon the morphological changes induced by neocarzinostatin in SK-N-SH cells. Both NGF and neocarzinostatin induced process outgrowth in these cells. These process formed in the presence of NGF however, were shorter and thinner than those induced by neocarzinostatin. Furthermore, only neocarzinostatin induced enlargement of the somata of the cells, and caused cell death in a concentration-dependent fraction of the culture. These distinguishing features of treated cells allowed us to determine whether or not NGF exposure altered responsiveness of the cells to neocarzinostatin. NGF (100–1000 ng/mL) protected SK-N-SH cells from the morphological and cytocidal effects of neocarzinostatin (1-hr exposure, 0.017 to 0.033 μg/mL). Protection from neocarzinostatin required that NGF be continuously present for a period beginning 24 hr prior to neocarzinostatin exposure and continuing for the duration of the experiment, implying that the protection afforded by NGF has a latency necessitating pretreatment, and is reversible. These results suggest that neocarzinostatin is taken up by the cells and can exert its effects once NGF is removed, even after neocarzinostatin is washed out of the medium. The signal transduction cascade triggered by NGF receptor binding may prevent the action of neocarzinostatin or the expression of the cellular changes induced in SK-N-SH cells by neocarzinostatin.