美洲大蠊多肽PAP-2对Balb/c裸鼠肝癌原位移植瘤缺氧微环境的影响  

Effect of Periplaneta Americana polypeptide PAP-2 on the hypoxic microenvironment of Balb/c nude mice with epatocellular carcinoma in situ transplanted tumors

作　　者：张俊秋 杜华钰 吴定宇 彭芳 ZHANG Jun-qiu;DU Hua-yu;WU Ding-yu;PENG Fang(College of Pharmacy,Dali University,Dali 671000,Yunnan Province,China;Yunnan Provincial Key Laboratory of Entomological Biopharmaceutical Research and Development,Dali 671000,Yunnan Province,China)

机构地区：[1]大理大学药学院,云南大理671000 [2]云南省昆虫生物医药研发重点实验室,云南大理671000

出　　处：《中国临床药理学杂志》2023年第13期1928-1932,共5页The Chinese Journal of Clinical Pharmacology

基　　金：国家自然科学基金资助项目(81560600)。

摘　　要：目的探讨美洲大蠊多肽PAP-2对肝癌缺氧微环境的影响,及其作用机制。方法BALb/c裸鼠用腋下接种HepG2肝癌细胞的方法构建肝癌原位移植瘤模型。将造模成功的裸小鼠随机分为模型组、阳性对照组(20 mg·kg^(-1)5-氟尿嘧啶)、CⅡ-3组(200 mg·kg^(-1)美洲大蠊提取物CⅡ-3)、脱脂膏组(200 mg·kg^(-1)美洲大蠊脱脂膏)和低、中、高剂量PAP-2组(50、100和200 mg·kg^(-1)美洲大蠊多肽PAP-2)及低、中、高剂量联合组(20 mg·kg^(-1)5-氟尿嘧啶+50、100和200 mg·kg^(-1)美洲大蠊多肽PAP-2),每组10只。各组小鼠均按0.1 mL·10 g^(-1)的剂量腹腔注射给药,除模型组和阳性对照组隔天1次外,其余各组每天1次,共计10 d。检测裸鼠移植瘤的抑瘤率和脏器指数,用实时荧光定量聚合酶链反应法检测肿瘤组织中缺氧诱导因子(HIF-1α)及血管内皮生长因子(VEGF)mRNA的表达水平。结果高剂量PAP-2组、高剂量联合组、CⅡ-3组、脱脂膏组和阳性对照组的抑瘤率分别为62.19%、78.07%、52.14%、51.11%和53.73%。高剂量PAP-2组、高剂量联合组、CⅡ-3组、脱脂膏组、阳性对照组和模型组的脾指数分别为(129.98±3.97)、(139.98±14.18)、(66.48±6.93)、(64.90±5.31)、(108.61±11.32)和(45.47±6.42)mg·g^(-1),肝指数分别为(843.10±59.41)、(1112.62±37.28)、(720.68±77.70)、(709.77±51.80)、(927.66±69.19)和(497.21±59.81)mg·g^(-1),HIF-1αmRNA表达量分别0.96±0.09、0.55±0.22、0.97±0.29、0.86±0.22、0.88±0.32和1.28±0.22,VEGF mRNA表达量分别为0.75±0.29、0.23±0.07、0.84±0.18、0.90±0.21、0.69±0.21和1.12±0.12。高剂量联合组、高剂量PAP-2组、CⅡ-3组、脱脂膏组和阳性对照组的上述指标与模型组比较,差异均有统计学意义(均P<0.05)。结论美洲大蠊多肽PAP-2通过抑制相关血管生成因子的表达水平,抑制肿瘤血管生成和肿瘤细胞迁移,改善肝癌缺氧微环境。Objective To investigate the effect and mechanism of action of Periplaneta Americana polypeptide PAP-2 on the hypoxia microenvironment of hepatocellular carcinoma.Methods The BALb/c nude mice model of orthotopic transplantation of hepatocellular carcinoma was established by inoculating HepG2 hepatocellular carcinoma cells under the armpit.The nude mice with successful model were randomly divided into model group,positive control group(20 mg·kg^(-1)5-fluorouracil),CⅡ-3 group(200 mg·kg^(-1)Periplaneta Americana extract CⅡ-3),skimmed cream group(200 mg·kg^(-1)Periplaneta Americana skimmed cream),PAP-2-L,-M,-H groups(50,100 and 200 mg·kg^(-1)Periplaneta Americana polypeptide PAP-2,respectively),combined-L,-M,-H groups(20 mg·kg^(-1)5-fluorouracil+50,100 and 200 mg·kg^(-1)Periplaneta Americana polypeptide PAP-2,respectively),with 10 mice per group.The mice in each group were injected intraperitoneally at a dose of0.1 m L·10 g^(-1).Except for the model and positive control groups were given once every other day,the other groups were given once a day,10 days in total.To detect the tumor inhibition rate of nude mice and the organ indexes.The expression levels of hypoxia inducible factor-1α(HIF-1α)and vascular endothelial growth factor(VEGF)mRNA in tumor tissue were detected by real-time quantitative polymerase chain reaction.Results The tumor inhibition rates of PAP-2-H,combined-H,CⅡ-3,skimmed cream and positive control groups were 62.19%,78.07%,52.14%,51.11%and 53.73%,respectively.The spleen indexes of PAP-2-H,combined-H,CⅡ-3,skimmed cream,positive control and model groups were(129.98±3.97),(139.98±14.18),(66.48±6.93),(64.90±5.31),(108.61±11.32)and(45.47±6.42)mg·g^(-1);the liver indexes were(843.10±59.41),(1112.62±37.28),(720.68±77.70),(709.77±51.80),(927.66±69.19)and(497.21±59.81)mg·g^(-1);the expression levels of HIF-1αmRNA were 0.96±0.09,0.55±0.22,0.97±0.29,0.86±0.22,0.88±0.32and 1.28±0.22;the expression levels of VEGF mRNA were 0.75±0.29,0.23±0.07,0.84±0.18,0.90±0.21,0.69±0.

关 键 词：美洲大蠊多肽PAP-2 肝癌 原位移植瘤 缺氧微环境 

分 类 号：R28[医药卫生—中药学]