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人肝癌细胞中热休克蛋白90的生物学特性

Biological characteristics of heat shock protein 90 in human liver cancer cells.

作者信息

Qin Li, Huang Haixin, Huang Jian, Wang Guodong, Huang Jinxin, Wu Xintian, Li Jinzhuan, Yi Weili, Liu Longjing, Huang Dongning

机构信息

Department of Oncology, Liuzhou Worker's Hospital Liuzhou, Guangxi, China.

出版信息

Am J Transl Res. 2019 Apr 15;11(4):2477-2483. eCollection 2019.

Abstract

Primary hepatic cancer refers to a malignant tumor that enables lethal cancero-metastasis. And hepatocellular carcinoma (HCC) is a most common cancer, accounting for around 75% of all cases. However, effective screening and diagnostic methods of HCC are limited currently. Heat shock protein 90 (HSP90), a sensitive biomarker, is found marked elevation in various malignancies. Thus, potential association between HSP90 expression and pathological onset of HCC is needed to be investigated. In current human study, plasma samples of advanced HCC patients were collected for biochemical assays, and cancer, non-cancer tissues from biopsy were stained immunohistochemically. In cell culture study, a human HepG2 cell line was subjected to a group of assays followed by HSP90 and inhibitor treatments. As results, the clinical data of HCC patients resulted in abnormal altered levels of serous molecules when compared to diagnostical references. However, these enzymatic changes showed no statistical significance. Significantly, plasma contents of HSP90 in HCC patients were elevated in comparison with those in HCC-free adults (<0.01). As shown in immunofluorescence stains, hepatocellular HSP90-labeled cells in alpha fetoprotein (AFP)-positive and negative HCC sections were obviously expressed. In cell culture data, HSP90-induced HepG2 cells resulted in increased cell proliferation, and proliferating cell nuclear antigen (PCNA)-, B-cell lymphoma 2 (Bcl-2)-positive cells (<0.05). In addition, HSP90 inhibitor-treated HepG2 cells showed effectively reduced cell growth, and PCNA-, Bcl-2-positive cell counts. Taken together, our current findings demonstrate that hepatocellular HSP90 may be positively involved in development of HCC, and it is likely a potential biomarker for monitoring advanced HCC.

摘要

原发性肝癌是指一种能够导致致命癌转移的恶性肿瘤。肝细胞癌(HCC)是最常见的癌症,约占所有病例的75%。然而,目前HCC的有效筛查和诊断方法有限。热休克蛋白90(HSP90)是一种敏感的生物标志物,在各种恶性肿瘤中发现其水平显著升高。因此,需要研究HSP90表达与HCC病理发生之间的潜在关联。在当前的人体研究中,收集了晚期HCC患者的血浆样本进行生化分析,并对活检得到的癌组织和非癌组织进行免疫组织化学染色。在细胞培养研究中,对人HepG2细胞系进行了一组分析,随后进行HSP90和抑制剂处理。结果显示,与诊断参考相比,HCC患者的临床数据导致血清分子水平异常改变。然而,这些酶学变化无统计学意义。值得注意的是,与无HCC的成年人相比,HCC患者血浆中HSP90的含量升高(<0.01)。如免疫荧光染色所示,在甲胎蛋白(AFP)阳性和阴性的HCC切片中,肝细胞HSP90标记的细胞明显表达。在细胞培养数据中,HSP90诱导的HepG2细胞导致细胞增殖增加,增殖细胞核抗原(PCNA)和B细胞淋巴瘤2(Bcl-2)阳性细胞增多(<0.05)。此外,HSP90抑制剂处理的HepG2细胞显示细胞生长有效降低,PCNA和Bcl-2阳性细胞计数减少。综上所述,我们目前的研究结果表明,肝细胞HSP90可能积极参与HCC的发展,并且很可能是监测晚期HCC的潜在生物标志物。

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