摘要
目的 探究美洲大蠊多肽PAE_(2)对HepG2/ADM移植瘤裸鼠凋亡蛋白表达及血管生成的影响。方法 将HepG2或HepG2/ADM细胞株接种于裸鼠皮下构建裸鼠肝癌皮下移植瘤模型。接种HepG2细胞的8只模型鼠为敏感组;接种HepG2/ADM细胞的模型鼠随机分为耐药组、阳性对照组和低、中、高剂量实验组,每组8只;另取8只正常裸鼠作为正常组。阳性对照组灌胃给予30 mg·kg^(-1)索拉非尼;低、中、高剂量实验组分别灌胃给予50,100和200 mg·kg^(-1)多肽PAE_(2);正常组、敏感组和耐药组均灌胃给予等量0.9%NaCl。7组裸鼠每天给药1次,连续给药14 d。测定肝指数及脾指数,用蛋白质印迹法检测B淋巴细胞瘤-2(Bcl-2)和Bcl-2相关X蛋白(Bax)的表达水平,用免疫组化法检测血管内皮生长因子(VEGF)蛋白的表达水平。结果 敏感组、耐药组、阳性对照组及低、高剂量实验组的肝指数分别为(73.37±0.08),(54.78±12.62),(49.88±6.54),(44.54±4.83)和(53.39±2.55)mg·g^(-1),脾指数分别为(10.87±1.08),(7.72±2.53),(5.43±0.99),(5.72±1.07)和(6.37±1.32)mg·g^(-1),Bax相对表达量分别为0.65±0.06,0.62±0.04,0.68±0.01,0.85±0.14和0.81±0.12,Bcl-2相对表达量分别为0.80±0.22,0.96±0.32,0.37±0.16,0.54±0.15和0.14±0.05,VEGF表达量分别为0.05±0.01,0.07±0.01,0.06±0.01,0.07±0.01和0.05±0.01。与耐药组相比,低剂量实验组的肝指数、脾指数、Bcl-2和VEGF表达量均显著降低,Bax表达量显著升高,差异均有统计学意义(均P<0.05)。结论 多肽PAE_(2)可通过促进移植瘤细胞凋亡及抑制肿瘤血管生成来逆转肝癌的多药耐药。
Objective To investigate the effect of Periplaneta americana polypeptide PAE_(2)on the expression of apoptosis protein and angiogenesis in nude mice with HepG2/ADM transplanted tumor.Methods HepG2or HepG2/ADM cells lines were inoculated subcutaneously in nude mice to establish the subcutaneously xenograft model of liver cancer.The 8model mice inoculated with HepG2 cells were the sensitive group,model mice inoculated with HepG2/ADM cells were randomly divided into drug resistance group,positive control group and experimental-L,-M,-H groups with 8 model mice per group.Another 8 normal nude mice were taken as the normal group.Positive control group was gavaged with 30mg·kg^(-1)of sorafenib.Experimental-L,-M,-H groups were gavaged with 50,100 and 200 mg·kg^(-1)PAE_(2),respectively.Normal group,sensitive group and drug resistance group were gavaged with an equal amount of 0.9%NaCl.Seven groups were administered once a day for 14 d.The liver index and spleen index were measured.Western blot was used to detect the expressions of B-cell lymphoma-2(Bcl-2) and B cell lymphoma-2 assaciated X (Bax) protein.Immunohistochemistry was used to detect the expression of vascular endothelial growth factor (VEGF).Results The liver indexes of sensitive group,drugresistant group,positive control group and experimental-L,-H groups were (73.37±0.08),(54.78±12.62),(49.88±6.54),(44.54±4.83) and (53.39±2.55) mg·g^(-1),the spleen indexes were (10.87±1.08),(7.72±2.53),(5.43±0.99),(5.72±1.07) and (6.37±1.32) mg·g^(-1),the relative expression of Bax protein were 0.65±0.06,0.62±0.04,0.68±0.01,0.85±0.14 and 0.81±0.12,the relative expression of Bcl-2protein were 0.80±0.22,0.96±0.32,0.37±0.16,0.54±0.15 and 0.14±0.05,the expression of VEGF were0.05±0.01,0.07±0.01,0.06±0.01,0.07±0.01 and 0.05±0.01,respectively.Compared with the drugresistant group,the liver index,spleen index and the expression levels of Bcl-2 and VEGF in experimental-L group decreased,the expression levels of Bax in experimental-L group increased,the differences were statistically significant (all P<0.05).Conclusion Polypeptide PAE_(2)can reverse the multi-drug resistance of liver cancer by promoting the apoptosis of transplanted tumor cells and inhibiting tumor angiogenesis.
作者
欧玲
吴定宇
吕鸿
李银蕊
彭芳
OU Ling;WU Ding-yu;LU Hong;LI Yin-rui;PENG Fang(College of Pharmacy,Dali University,Dali 671000,Yunnan Province,China;Laboratory Animal Facility,Dali University,Dali 671000,Yunnan Province,China)
出处
《中国临床药理学杂志》
CAS
CSCD
北大核心
2022年第6期560-564,共5页
The Chinese Journal of Clinical Pharmacology
基金
国家自然科学基金资助项目(81560600)
云南省应用基础研究重点基金资助项目(2017FH001-010)。
关键词
美洲大蠊多肽PAE_(2)
凋亡
血管生成
多药耐药
Periplaneta americana polypeptide PAE_(2)
apoptosis
angiogenesis
multi-drug resistance
