SERPING1 通过 ERK-MMP2-MMP-9 级联降低索拉非尼耐药肝细胞癌的细胞迁移率

IF 4.4 3区 医学 Q2 ENVIRONMENTAL SCIENCES
Ching-Chuan Hsieh, Yuh-Harn Wu, Yi-Li Chen, Chun-I Wang, Chao-Jen Li, I-Hsiu Liu, Chen-Wei Chou, Yang-Hsiang Lin, Po-Shuan Huang, Te-Chia Huang, Cheng-Yi Chen
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引用次数: 0

摘要

肝细胞癌(HCC)是最常见的原发性肝脏恶性肿瘤,死亡率在台湾所有恶性肿瘤中排名第二。索拉非尼(Sorafenib)是一种多重酪氨酸激酶抑制剂,可通过不同途径抑制肿瘤细胞增殖和肿瘤周围血管生成。然而,接受索拉非尼治疗的晚期HCC患者的生存结果仍不令人满意。遗憾的是,迄今为止还没有适用于临床的生物标志物来预测索拉非尼对HCC的治疗效果。我们发现,丝氨酸肽酶抑制剂 G 族成员 1(SERPING1)与 HCC 患者的总生存率和无复发生存率高度相关,并且与多个临床参数高度相关。索拉非尼增加了 SERPING1 在 HCC 细胞提取物和条件培养基中的表达,在耐索拉非尼的 HepG2 和 Huh7 细胞中也观察到了这一现象。索拉非尼降低了细胞活力和迁移,这与 SERPING1 在 HCC 进展中的作用相似。此外,索拉非尼还能抑制 HCC 细胞中 MMP-2 和 MMP-9 的活性,并增强 p-ERK 的表达。总之,索拉非尼可能通过上调SERPING1,通过p-ERK-MMP-2-MMP-9级联反应来降低HCC癌的进展。本研究探讨了 SERPING1 的作用和分子机制,以及其作为预测 HCC 患者索拉非尼耐药和进展的标志物的价值。本研究的结果有助于深入了解 SERPING1 在 HCC 索拉非尼耐药中的作用,可用于开发早期诊断和预后评估方法,并建立专门治疗 HCC 的新型治疗靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
SERPING1 Reduces Cell Migration via ERK-MMP2-MMP-9 Cascade in Sorafenib- Resistant Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the most common primary hepatic malignant tumor, and it ranks 2nd in terms of mortality rate among all malignancies in Taiwan. Sorafenib is a multiple tyrosine kinase inhibitor that suppresses tumor cell proliferation and angiogenesis around tumors via different pathways. However, the survival outcome of advanced HCC patients treated with sorafenib is still unsatisfactory. Unfortunately, there are no clinically applicable biomarkers to predict sorafenib therapeutic efficiency in HCC thus far. We found that serpin peptidase inhibitor, clade G, member 1 (SERPING1) is highly associated with overall and recurrence-free survival rates in HCC patients and is also highly correlated with several clinical parameters. SERPING1 expression was increased with sorafenib in both the HCC cell extract and conditioned medium, which was also observed in sorafenib-resistant HepG2 and Huh7 cells. Sorafenib decreased cell viability and migration, which was similar to the effect of SERPING1 in HCC progression. Moreover, sorafenib inhibited both MMP-2 and MMP-9 activity and enhanced the expression of p-ERK in HCC cells. In summary, sorafenib reduces HCC cancer progression might through the p-ERK-MMP-2-MMP-9 cascade via upregulation of SERPING1. In the present study, the roles and molecular mechanisms of SERPING1 and its value as a marker for predicting sorafenib resistance and progression in HCC patients were examined. The results of the present study provide a deep understanding of the roles of SERPING1 in HCC sorafenib resistance, which can be applied to develop early diagnosis and prognosis evaluation methods and establish novel therapeutic targets for specifically treating HCC.

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来源期刊
Environmental Toxicology
Environmental Toxicology 环境科学-毒理学
CiteScore
7.10
自引率
8.90%
发文量
261
审稿时长
4.5 months
期刊介绍: The journal publishes in the areas of toxicity and toxicology of environmental pollutants in air, dust, sediment, soil and water, and natural toxins in the environment.Of particular interest are: Toxic or biologically disruptive impacts of anthropogenic chemicals such as pharmaceuticals, industrial organics, agricultural chemicals, and by-products such as chlorinated compounds from water disinfection and waste incineration; Natural toxins and their impacts; Biotransformation and metabolism of toxigenic compounds, food chains for toxin accumulation or biodegradation; Assays of toxicity, endocrine disruption, mutagenicity, carcinogenicity, ecosystem impact and health hazard; Environmental and public health risk assessment, environmental guidelines, environmental policy for toxicants.
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