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花生四烯酸代谢与宫颈癌的关联研究

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目的 探究花生四烯酸(arachidonic acid,AA)代谢与宫颈癌的关联研究,为宫颈癌的代谢疗法提供新思路.方法 采用CCK-8法、细胞划痕实验分别检测AA干预后宫颈癌细胞的活性、迁移能力;采用GEPIA 2、GSCA数据库进行生物信息学分析,研究AA代谢关键酶与宫颈癌进展、预后、通路激活和肿瘤免疫的相关性;采用实时荧光定量聚合酶链反应(real-time fluorescence quantitative polymerase chain reaction,RT-qPCR)检测炎性细胞因子白细胞介素-6(interleukin-6,IL-6)、单核细胞趋化蛋白-1(monocyte chemoattractant protein-1,MCP-1)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、γ-干扰素(interferon-γ,IFN-γ)、环氧化酶 2(cyclooxygenase 2,COX2)、花生四烯酸脂加氧酶 15(arachidonic acid lipoxygenase 15,ALOX15)的mRNA表达情况.结果 5µmol/ml的AA能显著促进宫颈癌细胞生长(t=7.672,P=0.0166),且同浓度下,细胞相对迁移率提高了 30%(t=6.672,P=0.0026),炎性细胞因子的表达水平差异也有统计学意义(P<0.05).进一步通过生物信息学分析发现,AA代谢关键酶COX2、ALOX15在宫颈癌中的表达水平显著上调(P<0.05),且不同分期中的表达有所差异,并增加患者不良预后的风险.其中,COX2可能通过降低酪氨酸激酶代谢水平,加重DNA损伤,加速宫颈癌进展.ALOX15可能通过提高静息CD8+T细胞、B淋巴细胞浸润程度形成肿瘤炎性环境.结论 AA代谢能促进宫颈癌细胞的增殖与迁移,并引起肿瘤炎性微环境的改变,其代谢关键酶COX2、ALOX15在其中可能起重要作用.
Association between Arachidonic Acid Metabolism and Cervical Cancer
Objective To explore the association between arachidonic acid(AA)metabolism and cervical cancer(CC),to provide new ideas for metabolic therapies for CC.Methods The activity and migration ability of CC cells after AA intervention were detected by CCK-8 assay and cell scratch assay,respectively.Bioinformatics analysis was performed using GEPIA 2 and GSCA databases to study the correlation between key enzymes of AA metabolism(COX2,ALOX15)and the progression,prognosis,pathway activation,and tumor immunity of CC.The mRNA expression of inflammatory factors interleukin-6(IL-6),monocyte chemoattractant protein-1(MCP-1),tumor necrosis factor-α(TNF-α),interferon-γ(IFN-γ),cyclooxygenase 2(COX2),and arachidonic acid lipoxygenase 15(ALOX15)were detected by real-time fluorescence quantitative polymerase chain reaction(RT-qPCR).Results A A at 5μmol/ml significantly promoted the growth of CC cells(t=7.672,P=0.0166)and increased the relative cell migration rate by 30%at the same concentration(t=6.672,P=0.0026).And the expression levels of inflammatory factors also showed significant differences(P<0.05).Further bioinformatics analysis revealed that the expression levels of key enzymes of AA metabolism,COX2 and ALOX15,were significantly up-regulated in CC(P<0.05),which also different in different stages and increased the risk of poor prognosis in patients.Among them,COX2 may accelerate the progression of CC by decreasing the level of tyrosine kinase metabolism and exacerbating DNA damage,and ALOX15 may form a tumor inflammatory environment by increasing the degree of infiltration of resting CD8+T cells and B lymphocytes.Conclusion AA metabolism promotes the proliferation and migration of CC cells and induces changes in the tumor inflam-matory microenvironment,in which its metabolic key enzymes,COX2 and ALOX15,may play an important role.

Arachidonic acidTumor microenvironmentMetabolismCervical cancer

彭歆瑞、贾贞、祁凤仙、陆牡丹、陈道桢

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230032 安徽医科大学公共卫生学院毒理系

810904 海东市第二人民医院

214002 无锡,江南大学附属妇产医院(无锡市妇幼保健院)

花生四烯酸 肿瘤微环境 代谢 宫颈癌

2024

医学研究杂志
中国医学科学院

医学研究杂志

CSTPCD
影响因子:0.702
ISSN:1673-548X
年,卷(期):2024.53(12)