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Overcome of drug resistance using agents involving transcription factor expression in drug resistant human cancer cells

使用涉及耐药人类癌细胞中转录因子表达的药物克服耐药性

基本信息

批准号：
09670195
负责人：
FUKUDA Takeaki
金额：
$ 0.38万
依托单位：
Fukushima medical University School of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1998
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09670195/
关键词：
Drug resistance Transcription factor apoptosis heat shock protein NF-KB 熱ショック蛋白 TNFα

项目摘要

In this study the overcome of drug resistance by some agents having a inhibitory effect on the expression of transcription factors (TFs) has been evaluated on various types of drug resistant human cancer cell lines. In drug-sensitive cell lines, the activity of NF-kappa B was induced by tumor necrosis factor alpha and interferon gamma and apoptosis was induced. Pentoxyfilline, aspirin and acetyl cysteine can inhibit the activity of NF-kappa B but apoptosis was induced. In drug resistant cell lines, the activity of NF-kB was elevated under normal culture condition. It was inhibited by the agents described above and moderate overcome of drug resistance was achieved. In AraC resistant cell lines, NF-kB as well as Sp-1 and Sp-2 were activated, suggesting an important role in AraC resistance. Pentoxyfilline and FK506 inhibited the activity of these TFs but levels of drug resistance was slightly overcame. In drug resistant cell lines, elevated expression of heat shock proteins (HSPs) was observed in both cytoplasm and nucleus, suggesting a role in drug resistance with unknown mechanism. Pentoxyfilline and FK506 decreased the expression of HSPs and enhanced anticancer effect slightly. Further study is needed to elucidate whether these agents affect HSPs directly or through TBS.The combination with anticancer drugs and agents inhibiting TFs may be effective for overcome drug resistance.

本研究在不同类型的耐药人癌细胞系上评价了一些抑制转录因子表达的药物对耐药的克服作用。在药物敏感细胞系中，肿瘤坏死因子α和干扰素γ诱导NF-kappa B活性，诱导细胞凋亡。戊氧菲林、阿司匹林和乙酰半胱氨酸均能抑制nf - κ B的活性，但诱导细胞凋亡。在耐药细胞系中，正常培养条件下NF-kB活性升高。上述药物对其有抑制作用，达到了适度的耐药。在AraC耐药细胞系中，NF-kB以及Sp-1和Sp-2被激活，提示其在AraC耐药过程中起重要作用。Pentoxyfilline和FK506抑制了这些tf的活性，但耐药水平略有克服。在耐药细胞系中，细胞质和细胞核中均观察到热休克蛋白（HSPs）的表达升高，提示其在耐药过程中起作用，但机制未知。Pentoxyfilline和FK506均能降低HSPs的表达，增强其抗癌作用。这些药物是直接作用于热休克蛋白还是通过TBS作用于热休克蛋白，尚需进一步研究。与抗癌药物和抑制tf的药物联合使用可能是克服耐药性的有效方法。