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The Studies of Chlorogenic Acid Antitumor Mechanism by Gene Chip Detection: The Immune Pathway Gene Expression

机译:基因芯片检测的绿原酸抗肿瘤机制研究:免疫途径基因表达

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摘要

Persistently increasing incident of cancer in human beings has served to emphasize the importance of studies on mechanism of antitumor substances. Chlorogenic acid (CA), extracted from folium cortex eucommiae, has been confirmed to have lots of biological activities encompassing inhibition of tumor. However, the anticancer mechanism of CA remains unclear. Here, we have utilized a whole mouse genome oligo microarray (4*44K) to analyze gene expression level of female BALB/c mice (implanted with EMT-6 sarcoma cells) after treatment with low, medium, and high-dose CA (5 mg/kg, 10 mg/kg, and 20 mg/kg), docetaxel, interferon, and normal saline separately at 6 time points (3rd, 6th, 9th, 12th, 15th, and 18th days after administration). Differentially expressed genes screened out by time-series analysis, GO analysis, and pathway analysis, and four immune-related genes were selected for further confirmation using RT-qPCR. The results demonstrated that CA is able to change gene expression and that the responsive genes (CaN, NFATC2, NFATC2ip, and NFATC3) involved in immune pathways had been significantly upregulated by CA. Expression of immune factors such as IL-2R and IFN-γ can be improved by CA to promote activation and proliferation of T cells, macrophages, and NK cells, thus enhancing their surveillance and killing abilities, further suppressing the growth rate of tumor cells.
机译:持续增加人类中癌症事件的事件,以强调研究抗肿瘤物质机制的重要性。从叶片Cortex eucommiae中提取的绿原酸(CA)已被证实有许多生物活性包括抑制肿瘤。然而,CA的抗癌机制仍然不清楚。在这里,我们利用了整个小鼠基因组寡核微阵列(4 * 44K),以分析用低,培养基和高剂量CA处理(5份)后分析雌性BALB / C小鼠(植入EMT-6 SARCOMA细胞)的基因表达水平(5 Mg / kg,10 mg / kg和20 mg / kg),多西紫杉醇,干扰素和常生盐水在6个时间点(3号,第6,第6,第12次,第15天和给药后第18天)。通过时间序列分析,去分析和途径分析筛选的差异表达基因,并选择使用RT-QPCR进一步确认进行四种免疫相关基因。结果表明,CA能够改变基因表达,并且CA可以显着上调涉及免疫途径的响应基因(CAN,NFATC2,NFATC2IP和NFATC3)。 CA可以改善免疫因子如IL-2R和IFN-γ的表达,以促进T细胞,巨噬细胞和NK细胞的活化和增殖,从而提高其监测和杀伤能力,进一步抑制肿瘤细胞的生长速率。

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