中国普外基础与临床杂志

中国普外基础与临床杂志

肝细胞癌缺氧微环境的研究进展

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目的 了解缺氧微环境与肝细胞癌(HCC)的发生及发展之间的关系。 方法 复习近年来关于缺氧微环境与 HCC 关系研究的相关文献并进行分析。 结果 缺氧微环境在诱导 HCC 细胞耐药、血管形成等多个方面发挥着重要作用,是影响肿瘤代谢、侵袭及迁移能力的重要因素。缺氧微环境能上调缺氧诱导因子(HIF)的表达且促使其转录活性增强,促使血管内皮生长因子基因超常表达,调控肿瘤组织内新生血管生成。其中 HIF-1α 在调节血管新生、免疫逃逸、肿瘤侵袭及转移相关基因表达中起主要作用,还参与糖酵解,调节赖氨酰氧化酶 2 等进而调节上皮细胞-间充质转化过程,参与 HCC 细胞的侵袭和转移;HIF-2α 为一种恶性表型的关键调节因子,参与细胞增殖、血管生成和凋亡、代谢、转移和对化疗的抵抗。缺氧微环境为 HCC 治疗带来困难,但同时也是其潜在的治疗突破点。 结论 缺氧微环境能够通过多种机制促进 HCC 的侵袭、转移,其为 HCC 的临床治疗提供了新的靶点和策略。

Objective To investigate relationship between hypoxia microenvironment and occurrence and development of hepatocellular carcinoma (HCC). Method The relevant literatures on researches of the relationship between the hypoxic microenvironment and the HCC were review and analyzed. Results The hypoxia microenvironment played an important role in inducing the drug resistance and angiogenesis of the HCC cells, and it was an important factor of affecting the ability of tumor metabolism, invasion, and migration. The hypoxia microenvironment could up-regulate the expression of hypoxia-inducible factors (HIFs) and promote its transcriptional activity, promote the expression of vascular endothelial growth factor gene, and regulate the neovascularization in the tumor. Among them, the HIF-1α played a major role in regulating angiogenesis, immune escape, tumor invasion and metastasis-related gene expression, participating in the glycolysis, regulating lysyl oxidase 2 and thus regulated epithelial-mesenchymal transition, then promoted the invasion and metastasis of the HCC; HIF-2α was a key regulator of the malignant phenotype involving in the cell proliferation, angiogenesis, apoptosis, metabolism, metastasis, and resistance to chemotherapy. The hypoxia microenvironment posed some difficulties for the treatment of HCC, but it was also a potential therapeutic breakthrough. Conclusion Hypoxia microenvironment can promote invasion and metastasis of HCC through various mechanisms, which provides new targets and strategies for clinical treatment of HCC.

关键词: 肝细胞癌; 肿瘤微环境; 缺氧

Key words: hepatocellular carcinoma; tumor microenvironment; hypoxia

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