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小热休克蛋白hsp27作为人喉癌HEp-2细胞中细胞间黏附诱导耐药性的可能介质。

Small heat shock protein hsp27 as a possible mediator of intercellular adhesion-induced drug resistance in human larynx carcinoma HEp-2 cells.

作者信息

Mazurov Vladimir V, Solovieva Marina E, Leshchenko Violetta V, Kruglov Alexey G, Edelweiss Eveline F, Yakubovskaya Raisa I, Akatov Vladimir S

机构信息

Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, Pushchino, Russia.

出版信息

Biosci Rep. 2003 Aug;23(4):187-97. doi: 10.1023/b:bire.0000007692.59551.d8.

Abstract

The confluence-dependent resistance of human larynx carcinoma HEp-2 cells to hydrogen peroxide and a new antitumor drug based on the combination of vitamins C and B12b was studied. It was found that this resistance in growing cells is suppressed by the disruption of intercellular contacts by EGTA and is related neither to the activity of P-glycoprotein nor to the content of intracellular glutathione and the activities of glutathione S-transferases, glutathione peroxidase and glutathionine reductase. Here we showed that the level of expression of the small heat shock protein hsp27, which is known to protect cells from a variety of stresses associated with apoptosis, in growing confluent cells both in the presence and absence of the vitamins B12b and C is much higher (about 20-25 times) than in non-confluent cells. Taken together, the results suggest that the confluence-dependent resistance of cells to the combination of vitamins C and B12b and to hydrogen peroxide is mediated by hsp27 overexpression, which is activated via cell-cell adhesion.

摘要

研究了人喉癌HEp-2细胞对过氧化氢以及基于维生素C和维生素B12b组合的新型抗肿瘤药物的汇合依赖性抗性。发现通过EGTA破坏细胞间接触可抑制生长细胞中的这种抗性,且其既与P-糖蛋白的活性无关,也与细胞内谷胱甘肽的含量以及谷胱甘肽S-转移酶、谷胱甘肽过氧化物酶和谷胱甘肽还原酶的活性无关。在此我们表明,已知可保护细胞免受与凋亡相关的各种应激的小热休克蛋白hsp27的表达水平,在存在和不存在维生素B12b和C的情况下,生长汇合细胞中的表达水平均比未汇合细胞高得多(约20 - 25倍)。综上所述,结果表明细胞对维生素C和B12b组合以及过氧化氢的汇合依赖性抗性是由hsp27过表达介导的,hsp27过表达通过细胞 - 细胞黏附被激活。

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