INHIBITION OF PROLIFERATION AND INDUCTION OF APOPTOSIS BY ABROGATION OF HEAT-SHOCK PROTEIN (HSP)-70 EXPRESSION IN TUMOR-CELLS
INHIBITION OF PROLIFERATION AND INDUCTION OF APOPTOSIS BY ABROGATION OF HEAT-SHOCK PROTEIN (HSP)-70 EXPRESSION IN TUMOR-CELLS
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DOI：
10.1007/s002620050146
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发表时间：
1995-02-01
影响因子：
5.8
通讯作者：
UCHIDA, A
中科院分区：
文献类型：
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作者：
WEI, YQ;ZHAO, X;UCHIDA, A
肿瘤细胞通常表达升高水平的热休克蛋白（HSP）70。本研究旨在研究HSP70在人体系统中肿瘤细胞增殖和存活中的作用。当 Molt-4 和其他肿瘤细胞在体外用 HSP70 反义寡聚物处理时，它们显示出碘化丙啶染色的凝聚核（完整或碎片）。在琼脂糖凝胶电泳中，用 HSP70 反义寡聚物处理的肿瘤细胞观察到 DNA 片段的梯状图案，这与核小体间 DNA 片段化一致。流式细胞术分析揭示了反义寡聚物处理的细胞中碘化丙啶染色的细胞核的亚二倍体 DNA 峰。 HSP反义寡聚物诱导的细胞凋亡具有剂量和时间依赖性。反义寡聚物主要诱导G1期和S期肿瘤细胞凋亡，从而抑制细胞增殖。 HSP70 反义寡聚体引起 HSP70 表达的 DNA 序列特异性抑制，这发生在明显的细胞凋亡之前。这些结果表明HSP70反义处理抑制HSP70的表达，进而抑制细胞增殖并诱导肿瘤细胞凋亡，并表明HSP70是肿瘤细胞在正常条件下增殖和存活所必需的。
Tumor cells often express elevated levels of heat-shock protein (HSP) 70. The present study was designed to invesitgate the role of HSP70 in the proliferation and survival of tumor cells in the human system. When Molt-4 and other tumor cells were treated in vitro with HSP70 antisense oligomer, they displayed propidium-iodide-stained condensed nuclei (intact or fragmented). A ladder-like pattern of DNA fragments was observed with HSP70 antisense-oligomer-treated tumor cells in agrose gel electrophoresis, which was consistent with internucleosomal DNA fragmentation. Flow cytometry analysis revealed the hypodiploid DNA peak of propidium-iodide-stained nuclei in the antisense-oligomer-treated cells. The apoptosis induced by HSP antisense oligomer was dose- and time-dependent. The antisense oligomer induced apoptosis mainly in tumor cells at G1 and S phase, resulting in an inhibition of cell proliferation. HSP70 antisense oligomer caused DNA-sequence-specific inhibition of HSP70 expression, which preceded apparent apoptosis. These results indicate that HSP70 antisense treatment inhibits the expression of HSP70, which in turn inhibits cell proliferation and induces apoptosis in tumor cells and suggest that HSP70 is required for tumor cells to proliferate and survive under normal condition.