| Objective:Cancer is a kind of unlimited proliferation disease. The excessive proliferation will inevitably result in a serious imbalance between local tissue hypoxia and energy supply and will always grow in hypoxia, ischemia micro-environment. Therefore hypoxia is one of the main growth characteristics of entities tumor, and is closely related to tumor apoptosis, blood supply, invasion and metastasis. Reduce the ability of tumor cells to adapt hypoxia and inhibit their ability of anti-apoptotic properties, will be beneficial to inhibit tumor growth and metastasis. As is known, hypoxia-inducible factor-1 (hypoxia inducible factor-1, HIF-1) play a central role in tumor hypoxia regulation. HIF-1 is a nuclear transcription regulation factor which can transmit hypoxia signal, Regulated by hypoxia HIF-1 regulate transcription by binding sequence-specific DNA of target genes. It has been reported that in hypoxic conditions, HIF-1 reduce tissue damage by stimulating the activity of target gene-HO-1, and then reducing the synthesis of inflammatory chemokine. Heme oxygenase-1 (heme oxygenase-1, HO-1), also known as heat shock protein 32 (hot shock protein 32, HSP32), is rate-limiting enzyme in the process of heme degradation, can be induced by a variety of factors such as inflammatory factors, oxidation, ischemia, hypoxia, endotoxin, etc.. Heme oxygenase-1 (HO-1) as a highly conserved stress protein, can protect the organs, tissues and cells to resist injury caused by a variety of stimulating factors and pathological process, but this protective effect are non-selective, HO-1 can protect normal tissues and organs, but also can protect the tumor cells. At Cancer treatment, this protective effect is undesirable. The current study found that a high level HO-1 expression can be detected in a variety of human body tumor tissues, HO-1 induction and physical activity is closely related to tumor growth. Chemotherapy and radiotherapy can also stimulate overexpression of HO-1 in tumor tissue, HO-1 through its anti-stress effect exert its protective effect at cellular level against mass destruction of chemotherapy and radiotherapy to the tumor, which may also be one of mechanism that Cancer emerge drug resistance against Chemotherapy. Ho-1 has been known as a HIF-1 downstream gene, but there has been not much reports about HO-1 in what way impact on HIF-1. Studying the impact of HO-1 activity on HIF-1, and further exploring the relationship between HO-1,HIF-1 and tumor occurrence and development, will provide a theoretical foundation for tumor pathogenesis and treatment explorationMethods:Hypoxia-inducible models of gastric cancer cell lines were set up. Three groups were assigned:Group Z, Using RNA interference technology to suppress the gene expression of HO-1 to reduce its activity; Group H, Hemin was used to promote the expression of HO-1; Group D, as control group. Using RT-PCR technique in each group to determine mRNA levels of HO-1 and HIF-1; Using immunohistochemical technique in each group to detect protein levels of HO-1 and HIF-1; The experimental data were expressed with (χ±s) and analysed by SPSS 12.0 statistic software.Results:The mRNA and protein level of HO-1 and HIF-1 in Group Z was significantly lower than that in the control group; Whereas, in Group H,the protein and mRNA level of HO-1 and HIF-1 was significantly higher than that in the control group.Conclusions:Decreasing HO-1 activity through gene disruption technology can reduce the expression of HIF-1 in mRNA and protein; Whereas increasing HO-1 activity through Hemin-induced can enhance the expression of HIF-1 in mRNA and protein. In other words, HO-1 is in regulation of HIF-1, at the same time, HO-1 plays a positive feedback role on the expression of HIF-1. This will provide rationale and experimental basis for the treatment to malignant tumors through gene technology such as RNA interference. |
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