首页|地塞米松对肝癌微循环及能量代谢影响机制的研究

地塞米松对肝癌微循环及能量代谢影响机制的研究

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探讨地塞米松对肝癌微循环血管生成及能量代谢的影响。通过绿色荧光蛋白GFP标记肝癌HepG2细胞,原位移植法建立原位肝模型,荧光成像系统观察地塞米松对裸鼠肿瘤负荷情况;建立金黄地鼠颊囊肝癌模型,微循环活体观测显微镜记录给药周期内模型鼠微循环生长状态及肿瘤生长情况;免疫印迹试验检测小鼠肝癌H22细胞不同给药浓度下糖异生关链酶PEPCK、G6Pase蛋白的表达情况;建立小鼠肝癌移植瘤模型,WB法检测PEPCK、G6Pase表达情况,双抗酶联免疫吸附法(ELISA)检测血管内皮生长因子(VEGF)表达情况。结果显示:1。裸鼠原位肝癌模型对照组小鼠体重增长了27。3%,肝癌面积增长了6。7倍;而地塞米松给药组小鼠体重只增长了0。3%,肝癌面积仅增长了4。7倍。2。金黄地鼠颊囊肝癌模型新生瘤体明显,血管明显比正常组多;地塞米松治疗组血管增长缓慢,7 d仅增长4。2%,其肿瘤体积也明显变小。3。不同浓度地塞米松处理肝癌H22细胞后,PEPCK、G6Pase的表达量随给药浓度增加逐渐升高。4。地塞米松小鼠肝癌移植瘤,PEPCK、G6Pase随给药浓度的增加表达量逐渐升高,蛋白表达量超过正常组的50%;与对照组相比,实验组VEGF的表达量明显降低,与给药浓度成反比。地塞米松对肝癌的生长具有显著的抑制功能,推测其调控机理可能是,一方面通过促进肝癌细胞内的糖异生过程,抑制其能量代谢;另一方面通过抑制血管内皮生长因子的表达,减少血管生成和能量供应;两条调控通路均能达到抑制肿瘤生长的目的。
Study on the Mechanism of Dexamethasone on Microvessel and Energy Metabolism in Hepatocellular Carcinoma
To investigate the effect of dexamethasone on microcirculation angiogenesis and energy metabolism in hepatocellular car-cinoma,HepG2 cells of liver cancer were labeled with green fluorescent protein GFP.The orthotopic liver model was established by orthotopic transplantation.The tumor load of dexamethasone in nude mice was observed by fluorescence imaging system.The golden hamster cheek pouch hepatoma model was established,and the microcirculation growth and tumor growth of the model mice during the drug administration period were recorded under the microscope.Western blot assay was used to detect the expression of gluconeo-genesis related chain kinase(PEPCK)and G6Pase protein in H22 cells of mice under different drug concentrations.The transplan-ted tumor model of liver cancer in mice was established.The expression of PEPCK and G6Pase was detected by WB method,and the expression of vascular endothelial growth factor(VEGF)was detected by double antibody enzyme-linked immunosorbent assay(ELISA).In the control group of nude mice with orthotopic liver cancer,the body weight increased by 27.3%,and the area of liver cancer increased by 6.7 times.In the dexamethasone group,the weight of mice increased by only 0.3%,and the area of liver cancer increased by only 4.7 times.The golden hamster cheek pouch hepatoma model had more tumor bodies and blood vessels than the normal group.The blood vessels in the dexamethasone treatment group grew slowly,only 4.2%after 7 days,and the tumor volume also decreased significantly.The expression of PEPCK and G6Pase in hepatoma H22 cells treated with different concentrations of dexamethasone gradually increased with the increase of drug concentration.The expression of PEPCK and G6Pase in liver cancer transplanted tumor of dexamethasone mice increased gradually with the increase of drug concentration,and the protein expression was 50%higher than that in normal group.Compared with the control group,the expression of VEGF in the experimental group was sig-nificantly reduced,which was inversely proportional to the drug concentration.Dexamethasone can significantly inhibit the growth of liver cancer.Its regulation mechanism may be:On the one hand,it can inhibit energy metabolism by promoting the gluconeogenesis in hepatoma cells;On the other hand,it can reduce angiogenesis and energy supply by inhibiting the expression of vascular endothelial growth factor;Both of the two pathways can inhibit tumor growth.

DexamethasoneGluconeogenesisAngiogenesisTumor inhibitionLiver cancerPEPCKG6Pase

许英、刘英、杨晓霞

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山东大学第二医院药学部药品供应科静配中心,山东济南 250033

地塞米松 糖异生 血管生成 肿瘤抑制 肝癌 PEPCK G6Pase

2024

药物生物技术
中国药科大学,中国医药科技出版社,中国药学会

药物生物技术

CSTPCD
影响因子:0.463
ISSN:1005-8915
年,卷(期):2024.31(1)
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