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肿瘤细胞在乏氧环境中会发生一系列生物学行为的改变,包括肿瘤侵袭性和转移能力的增加,其中乏氧诱导因子-1α(hypoxiainduciactor1α,HIF-1α)起关键作用。HIF-1α可作用于多个环节促进肿瘤转移。在细胞运动方面肝细胞生长因子(HGF)的受体c-Met在乏氧时增加,能促进细胞活动性并通过与肝细胞生长因子结合而增加细胞的侵袭性;基质降解方面肿瘤细胞侵袭转移能力与其产生或诱导MMPs的能力密切相关,HIF-1可引起MMPs的表达增加,进而促进恶性肿瘤的转移;细胞黏附方面HIF-1α可通过对肿瘤细胞黏附分子表达的影响而促进肿瘤转移;血管生成方面乏氧能引起VEGF表达的上调,在肿瘤发生早期向血管生成型转变过程中,HIF-1α介导了VEGF的上调;细胞凋亡方面HIF-1上调凋亡抑制因子Bcl-2,抑制凋亡,从而增强肿瘤转移力。HIF-1α亦可上调凋亡抑制因子p21,从而抑制凋亡使肿瘤恶性程度增加易于转移。对HIF-1α的研究可能是治疗肿瘤、减少恶性肿瘤转移的一种新途径。
Tumor cells undergo a series of biological behavioral changes in anoxic environment, including tumor invasion and metastasis, in which hypoxiainduciactor1α (HIF-1α) plays a key role. HIF-1α can act on multiple links to promote tumor metastasis. In cellular motion, the hepatocyte growth factor (HGF) receptor c-Met increases in hypoxia, promotes cell activity and increases cell invasiveness by binding to hepatocyte growth factor; invasion and metastasis of tumor cells in stromal degradation HIF-1 can increase the expression of MMPs, and then promote the metastasis of malignant tumor. In the aspect of cell adhesion, HIF-1α can promote the tumor metastasis by the influence on the expression of tumor cell adhesion molecules; Hypoxia can induce the up-regulation of VEGF expression in the early stage of tumorigenesis, HIF-1αmediated VEGF up-regulation; HIF-1 up-regulates apoptosis inhibitor Bcl-2 Apoptosis, thereby enhancing tumor metastasis. HIF-1α also up-regulates the inhibitor of apoptosis p21, thereby inhibiting apoptosis and increasing the malignant degree of the tumor. The study of HIF-1α may be a new way to treat tumors and reduce the metastasis of malignant tumors.