白屈菜碱对小鼠肺癌细胞皮下移植瘤生长和血管生成的抑制作用及其机制  

Inhibitory effect of leucovorin on growth and angiogenesis of subcutaneous transplanted tumors in mouse lung cancer cells and its mechanism

作　　者：金学军[1] 卢楚沅 JIN Xuejun;LU Chuyuan(Center for Molecular Drug Research,Yanbian University,Yanji 133002,China;Department of Dentistry,School of Medical Sciences,Yanbian University,Yanji 133002,China)

机构地区：[1]延边大学分子药物研究中心,吉林延吉133002 [2]延边大学医学院口腔医学系,吉林延吉133002

出　　处：《吉林大学学报（医学版）》2024年第3期612-619,共8页Journal of Jilin University：Medicine Edition

基　　金：国家自然科学基金项目(81660608)。

摘　　要：目的:探讨白屈菜碱对肺癌移植瘤小鼠肿瘤生长和血管生成的影响,并阐明其作用机制。方法:选取32只健康C57BL/6小鼠,制备Lewis肺癌移植瘤小鼠模型。将小鼠随机分为模型组(0.9%氯化钠)、低剂量白屈菜碱组(25 mg·kg^(-1)白屈菜碱)、高剂量白屈菜碱组(50 mg·kg^(-1)白屈菜碱)和阳性对照组(60 mg·kg^(-1)环磷酰胺),每组8只。称量各组小鼠移植瘤质量并计算抑瘤率,计算各组小鼠胸腺指数和脾脏指数,采用酶联免疫吸附测定(ELISA)法检测各组小鼠血清中白细胞介素2(IL-2)、γ干扰素(INF-γ)和肿瘤坏死因子α(TNF-α)水平,免疫组织化学法检测各组小鼠肿瘤组织中血管内皮生长因子(VEGF)蛋白表达情况并计算微血管密度(MVD)及VEGF蛋白表达评分,Westernblotting法检测各组小鼠肿瘤组织中核因子κB(NF-κB)和缺氧诱导因子1α(HIF-1α)蛋白表达水平。结果:与模型组比较,低和高剂量白屈菜碱组及阳性对照组小鼠移植瘤质量均降低(P<0.05);与低剂量白屈菜碱组比较,高剂量白屈菜碱组和阳性对照组小鼠移植瘤质量均降低(P<0.05),抑瘤率均升高(P<0.05);与高剂量白屈菜碱组比较,阳性对照组小鼠移植瘤质量均降低(P<0.05),抑瘤率升高(P<0.05)。与模型组比较,低和高剂量白屈菜碱组及阳性对照组小鼠脾脏指数和胸腺指数均升高(P<0.05);与低剂量白屈菜碱组比较,高剂量白屈菜碱组和阳性对照组小鼠脾脏指数及胸腺指数均升高(P<0.05);与高剂量白屈菜碱组比较,阳性对照组小鼠脾脏指数和胸腺指数均升高(P<0.05)。ELISA法,与模型组比较,低和高剂量白屈菜碱组及阳性对照组小鼠血清中IL-2、INF-γ和TNF-α水平均升高(P<0.05);与低剂量白屈菜碱组比较,高剂量白屈菜碱组和阳性对照组小鼠血清中IL-2、INF-γ和TNF-α水平均升高(P<0.05);与高剂量白屈菜碱组比较,阳性对照组小鼠血清中IL-2、INF-γ和TNF-α水平均升高(P<0.05)。与模型�Objective:To discuss the effects of leucovorin on tumor growth and angiogenesis in the mice with lung cancer transplantation tumor,and to elucidate its mechanism.Methods:Thirty-two healthy C57BL/6 mice were selected to prepare the Lewis lung cancer transplantation tumor models.The mice were randomly divided into model group(0.9% NaCl),low dose of leucovrin group(25 mg·kg~(-1)leucovrin),high dose of leucovrin group(50 mg·kg~(-1) leucovrin) and positive control group(60 mg·kg~(-1)cyclophosphamide),and there were 8 mice in each group.The levels of interleukin-2(IL-2),interferon-γ(INF-γ) and tumor necrosis factor-α(TNF-α) in serum of the mice in various groups were detected by enzyme linked immunosorbent assay(ELISA) method;the expression of vascular endothelial growth factor(VEGF) in tumor tissue of the mice in various groups were detected by immunohistochemistry,and the microvascular density(MVD) and VEGF protein expression scores were calculated;the expression levels of nuclear factor-κB(NF-κB) and hypoxia inducible factor-1α(HIF-1α) in tumor tissue of the mice in various groups were detected by Western blotting method.Results:Compared with model group,the transplantation tumor masses of the mice in low and high doses of leucovorin groups and positive control group were decreased(P<0.05);compared with low dose of leucovorin group,the transplantation tumor masses of the mice in high dose of leucovorin group and positive control group were decreased(P<0.05),and the tumor inhibitory rates were increased(P<0.05);compared with high dose of leucovorin group,the transplantation tumor mass of the mice in positive control group was decreased(P<0.05),and the tumor inhibitory rate was increased(P<0.05).Compared with model group,the spleen indexes and thymus indexes of the mice in low and high doses of leucovorin groups and positive control group were increased(P<0.05);compared with low dose of leucovorin group,the spleen indexes and thymus indexes of the mice in high dose of leucovorin group and positive control g

关 键 词：白屈菜碱 核因子ΚB 缺氧诱导因子1Α 肺癌移植瘤 血管生成 

分 类 号：R392[医药卫生—免疫学]