The relation of the anti-cancer drug resistance and heat shock protein 60 expression

抗癌耐药性与热休克蛋白60表达的关系

• 批准号: 07671826
• 负责人: KIMURA Eizo
• 金额: $ 1.41万
• 依托单位: Jikei 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: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07671826/
• 关键词: heat shock; hyperthermia; cancer; drug resistance; survival; anti-cancer drug; heat shock protein; 抗癌剤耐性; 卵巣がん; 免疫組織化学; heat shock; 熱ショック蛋白; シスプラチン; 培養細胞; mRNA

The expression of the 60-kDa heat-shock protein (HSP60) varies markedly among pateints with ovarian carcinoma, and high-level expression predicts poor survival in such patients treated with cisplatin (DDP)-containing chemotherapy programs. I investigated the expression of HSP60 in human ovarian carcinoma 2008 cells and an 11-fold DDP-resistant subline 2008/C13<@D1**@>D15.25. Heating for 2 h at 44ﾟC produced a 2.7(]SY.+-。[)0.16-fold increase (mean (]SY.+-。[)SD) that was maximal at 4 h after the start of heat exposure. Exposure to an IC50 concentration of DDP for 1 h induced a 1.8(]SY.+-。[)0.03-fold increase in hsp60 expression. The opposite was true for cadmimum and zinc, both of which induced increases in metallothionein IIA but not in the hsp60 message. 2008/C13<@D1**@>D15.25 cells cnstitutively overexpressed hsp60 mRNA by 1.7(]SY.+-。[)0.16 orders of magmitude and contained a 3.8(]SY.+-。[)0.45-fold higher level of HSP60as detected by immunocytochemical satining. 2008/C13<@D1**@>D15.25 cells showed 1.2-fold cross-resistance to thermal killing. Expression of hsp60 was markedly reducedin 2008 xenografts as compared with 2008 cells growing in-vitro ; however, neither serum starvation nor refeeding altered the message level. Exposure to a variety of growth factor and drug treatments known to alter the DDP sensitivity of2008 cells, including epidermal growth factor, 12-O-tetradecanoylphorbol-13-acetate, buthionine sulfoximine, ouabain, and forskolin, did not alter hsp60 expression. These results suggest a role for HSP60 in mediating resistance to both DDP and hyperthermia but indicate that the hsp60 mRNA levels are not regulated by the factors listed above.

60 kDa热休克蛋白(HSP60)的表达在卵巢癌患者中差异显著，高水平的表达预示着接受顺铂(DDP)化疗方案治疗的此类患者的生存率较低。我研究了HSP60在人卵巢癌2008细胞和11倍顺铂耐药亚系2008/C13&lt；D15.25中的表达。在44ﾟC加热2小时，得到2.7(]sy.+-。[)增长0.16倍(平均()SY+-。[SD])，在热暴露后4h达到最大。暴露于IC50浓度的顺铂1h，可诱发1.8(]sy.+-。[]Hsp60的表达增加0.03倍。镉和锌的情况正好相反，两者都能诱导金属硫蛋白IIA的增加，但在HSP60信息中不会。2008/C13&lt；d1**@&gt；D15.25细胞Hsp60mR-NA高表达1.7(]sy+-)。[)0.16目，含3.8(]sy.+-。[]免疫细胞化学染色检测到的HSP60水平高0.45倍。2008/C13&lt；d1**@&gt；D15.25细胞对热杀灭表现出1.2倍的交叉抗性。与在体外生长的2008细胞相比，HSP60在2008年异种移植中的表达显著降低；然而，血清饥饿和重新喂养都不会改变该消息的水平。暴露于各种已知可改变2008细胞对DDP敏感性的生长因子和药物治疗，包括表皮生长因子、12-O-十四酰佛波醇-13-乙酸酯、丁硫氨酸亚磺胺、哇巴因和Forsklin，不会改变Hsp60的表达。这些结果提示HSP60在介导对DDP和高温的抵抗中起作用，但表明HSP60的mRNA水平不受上述因素的调节。

项目成果

Yoshihiro Kikuchi(Ed.): "The Mechanism of Cisplatin Resistance and its Circumvention" Nova Science Publishers,Inc. (in print), (1998)

Yoshihiro Kikuchi（主编）：《顺铂耐药机制及其规避》Nova Science Publishers,Inc.

Yoshihiro Kikuchi(Ed.): "The Mechanism of Cisplatin Resistance and its Circumvention" Nova Science Publishers,Inc.(in print), (1998)

Yoshihiro Kikuchi（主编）：“顺铂耐药机制及其规避”Nova Science Publishers, Inc.（印刷版），（1998 年）