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

60 kda热休克蛋白（HSP60）的表达在卵巢癌患者中存在显著差异，高水平表达预示着接受含顺铂（DDP）化疗方案治疗的卵巢癌患者生存率较低。我研究了HSP60在人卵巢癌2008细胞和11倍ddp耐药亚系2008/C13<@ d1 **@>D15.25中的表达。在44℃下加热2小时，产生2.7(]SY.+-) .[)0.16倍(平均（]SY.+-）。[)SD)，在热暴露开始后4 h达到最大。暴露于IC50浓度的DDP 1小时后，hsp60的表达增加了1.8(]SY.+- -[)0.03倍。镉和锌的情况正好相反，两者都能引起金属硫蛋白IIA的增加，但hsp60信息没有增加。2008/C13<@ d1 **@>D15.25细胞组成性过表达hsp60 mRNA，表达量为1.7(]SY.+- - .[)0.16个数量级，免疫细胞化学染色检测hsp60 mRNA表达量为3.8(]SY.+- - -[)0.45倍。2008/C13<@ d1 **@>D15.25细胞对热杀伤表现出1.2倍的交叉抗性。与体外培养的2008细胞相比，2008异种移植物中hsp60的表达明显降低；然而，血清饥饿和再喂养都没有改变信息水平。暴露于多种已知会改变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 -十四烷酰磷-13-乙酸酯、丁硫氨酸亚砜胺、瓦巴因和福斯克林，没有改变hsp60的表达。这些结果表明HSP60在介导DDP和高温抵抗中发挥作用，但表明HSP60 mRNA水平不受上述因素的调节。

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.