连翘脂素调节HIF-1α/VEGF信号通路对宫颈癌细胞恶性生物学行为的影响  

Effect of phillygenin on the malignant biological behavior of cervical cancer cells by regulating the HIF-1α/VEGF signaling pathway

作　　者：申红梅 王丽霞 冯绪强 亓军波 侯学涛 SHEN Hongmei;WANG Lixia;FENG Xuqiaang;QI Junbo;HOU Xuetao(Department of Pharmacy,The Second Children&Women’s Healthcare of Jinan City,Jinan,Shandong 271100,China;Department of Children’s Rehabilitation,The Second Children&Women’s Healthcare of Jinan City,Jinan,Shandong 271100,China;Department of Pharmacy,Jinan Integrated Traditional Chinese and Western Medicine Hospital,Jinan,Shandong 271100,China;Department of Gynecology,The Second Children&Women’s Healthcare of Jinan City,Jinan,Shandong 271100,China)

机构地区：[1]济南市第二妇幼保健院药剂科,山东济南271100 [2]济南市第二妇幼保健院儿童康复科,山东济南271100 [3]济南市中西医结合医院药学部,山东济南271100 [4]济南市第二妇幼保健院妇科,山东济南271100

出　　处：《中国优生与遗传杂志》2024年第9期1820-1825,共6页Chinese Journal of Birth Health & Heredity

基　　金：济南市卫生健康委员会中医药科技计划专项项目(2022-中-13)。

摘　　要：目的探究连翘脂素(PHI)是否通过调节低氧诱导因子-1α(HIF-1α)/血管内皮生长因子(VEGF)信号通路进而影响宫颈癌细胞的恶性生物学行为。方法MTT检测不同浓度PHI处理HeLa细胞24 h的增殖情况和IC50,将HeLa细胞分为4组,常规培养的HeLa细胞记为Control组,50μmol/mL PHI处理记为50PHI组,100μmol/mL PHI处理记为100PHI组,100μmol/mL PHI+10μmol/L DMOG(HIF-1α/VEGF通路激活剂)处理记为100PHI+DMOG组。细胞克隆检测细胞增殖和集落形成能力;Transwell实验和细胞流式实验检测HeLa细胞的迁移、侵袭和凋亡率;蛋白质印迹(Western blot)实验检测信号通路相关蛋白HIF-1α、VEGF、COX-2、E-cadherin、N-cadherin的表达情况;HeLa细胞构建宫颈癌SD大鼠模型,记录宫颈癌肿瘤质量和体积大小,免疫组化检测HIF-1α、VEGF蛋白表达。结果与Control组相比,50PHI组和100PHI组细胞增殖、迁移、集落形成能力、侵袭,HIF-1α、VEGF、COX-2、N-cadherin蛋白表达显著降低(P<0.05),细胞凋亡和E-cadherin的蛋白表达显著升高(P<0.05);与100PHI组相比,100PHI+DMOG组细胞增殖、迁移、集落形成能力、侵袭,HIF-1α、VEGF、COX-2、N-cadherin蛋白表达显著升高(P<0.05),细胞凋亡和E-cadherin的蛋白表达显著降低(P<0.05)。与对照组相比,PHI组肿瘤质量、体积、HIF-1α阳性率、VEGF阳性率均显著降低(P<0.05)。结论PHI可以抑制宫颈癌细胞恶性生物学行为,其机制可能是通过调节HIF-1α/VEGF信号通路实现的。Objective To investigate whether phillygenin(PHI)affects the malignant biological behavior of cervical cancer cells by regulating the hypoxia inducible factor-1α(HIF-1α)/vascular endothelial growth factor(VEGF)signaling pathway.Methods MTT was applied to detect the proliferation and IC50 of HeLa cells after treating with different concentrations of PHI for 24 hours.HeLa cells were separated into four groups:the conventional cultured HeLa cells were labeled as the Control group,the HeLa cells treated with 50μmol/mL PHI were labeled as the 50PHI group,the HeLa cells treated with 100μmol/mL PHI were labeled as the 100PHI group,and the HeLa cells treated with 100μmol/mL PHI+10μmol/L DMOG(HIF-1α/VEGF pathway activator)were labeled as the 100PHI+DMOG group.Cell cloning was applied to detect cell proliferation and colony formation ability.Transwell experiments and cell flow cytometry were applied to detect the migration,invasion,and apoptosis rate of HeLa cells.Western blot experiments were applied to detect the expression of signaling pathway related proteins HIF-1α,VEGF,COX-2,E-cadherin,and N-cadherin.HeLa cells were used to construct a cervical cancer SD rat model,and the mass and volume of cervical cancer tumors were recorded.Immunohistochemistry was applied to detect the expression of HIF-1αand VEGF proteins.Results Compared with the Control group,the cell proliferation,migration,colony forming ability,invasion,HIF-1α,VEGF,COX-2,and N-cadherin protein expression reduced in the 50PHI and 100PHI groups(P<0.05),the apoptosis and E-cadherin protein expression increased(P<0.05).Compared with the 100PHI group,the cell proliferation,migration,colony forming ability,invasion,HIF-1α,VEGF,COX-2,and N-cadherin protein expression increased in the 100PHI+DMOG group(P<0.05),the cell apoptosis and E-cadherin protein expression reduced(P<0.05).Compared with the control group,the tumor mass,volume,HIF-1αpositive rate,and VEGF positive rate in the PHI group reduced(P<0.05).Conclusion PHI can inhibit the malignant biologi

关 键 词：连翘脂素 宫颈癌 低氧诱导因子-1α/血管内皮生长因子 恶性生物学行为 

分 类 号：R737.33[医药卫生—肿瘤]