摘要
目的探讨熊果酸(ursolic acid,UA)对结直肠癌小鼠移植瘤生长、炎症反应与血管新生的影响,为治疗结直肠癌提供实验依据。方法采用皮下注射结直肠癌HT-29细胞构建裸鼠结直肠癌移植瘤模型,随机分为对照组(Control组)与UA干预组(UA组);采用游标卡尺测量移植瘤体积;免疫组化法检测肿瘤组织Ki67、PIM-1、Bcl-2、Bax、FGFR、VEGFR等蛋白表达;Western bolt法检测细胞凋亡标志物caspase-3、caspase-9、PARP;Bio plex检测小鼠血清中VEGF、PDGF-BB含量与细胞炎症因子IL-1α、IL-4、IL-10,IL-6、TNF-α的含量。结果肿瘤大小变化:与Control组相比,UA干预后可降低肿瘤的体积(P<0.05)。肿瘤细胞增殖、凋亡情况变化:与Control组相比,UA组增殖标志物Ki67、抗凋亡蛋白PIM-1,Bcl-2表达降低,促凋亡蛋白Bax表达升高。细胞凋亡标志物Cytochrome C、caspase-3、caspase-9、PARP表达增加(P<0.05)。肿瘤炎症情况变化:与Control组相比,UA干预组中小鼠血清中细胞因子IL-1α、IL-6、TNF-α表达降低,IL-4、IL-10表达升高(P<0.05)。肿瘤组织中血管新生的情况:与Control组相比,UA干预后,肿瘤组织中VEGF、VEGFR、FGFR、PDGF-BB表达下降(P<0.05)。结论UA可抑制结直肠癌小鼠移植瘤生长、炎症反应与血管新生,可能与细胞凋亡通路、炎症通路、血管新生相关。
Objective:To study the effect of ursolic acid(UA)on the growth of transplanted tumors,inflammatory response and angiogenesis in mice with colorectal cancer,and to provide experimental evidence for the treatment of colorectal cancer.Methods:A nude mouse model of colorectal cancer transplanted tumors was constructed by subcutaneous injection of colorectal cancer HT-29 cells and randomly divided into the control group(Control group)and the UA intervention group(UA group).The volume of the transplanted tumor was measured using a vernier caliper.The protein expressions of Ki67,PIM-1,Bcl-2,Bax,FGFR,VEGFR,etc.in tumor tissues were detected by immunohistochemistry.The apoptotic markers caspase-3,caspase-9 and PARP were detected by Western bolt method.Bio plex was used to detect the contents of VEGF and PDGF-BB in the serum of mice and the contents of cellular inflammatory factors IL-1α,IL-4,IL-10,IL-6 and TNF-α.Results:Tumor size change:Compared with the Control group,UA intervention could reduce the tumor volume(P<0.05).Change in tumor cell proliferation and apoptosis:Compared with the Control group,the expressions of proliferation markers Ki67,anti-apoptotic proteins PIM-1 and Bcl-2 in the UA group decreased,while the expression of pro-apoptotic protein Bax increased.The expressions of apoptosis markers Cytochrome C,caspase-3,caspase-9 and PARP increased(P<0.05).Change in tumor inflammation:Compared with the Control group,the expressions of cytokines IL-1α,IL-6,and TNF-αin the serum of mice in the UA intervention group decreased,while the expressions of IL-4 and IL-10 increased(P<0.05).The situation of angiogenesis in tumor tissues:Compared with the Control group,after UA intervention,the expressions of VEGF,VEGFR,FGFR and PDGF-BB in tumor tissues decreased(P<0.05).Conclusion:UA can inhibit the growth of transplanted tumors,inflammatory response and angiogenesis in mice with colorectal cancer,which may be related to the apoptotic pathway,inflammatory pathway and angiogenesis.
作者
陈洋佚
贾沛芝
王敬婷
戴珍炜
黄志鸿
林久茂
CHEN Yang-yi;JIA Pei-zhi;WANG Jing-ting;DAI Zhen-wei;HUANG Zhi-hong;LIN Jiu-mao(Fujian University of Traditional Chinese Medicine,Fuzhou 350122,China;Fujian Key Laboratory of Integrated Traditional Chinese and Western Medicine for Geriatric Diseases,Fuzhou 350122,China;Key Laboratory of Integrated Traditional Chinese and Western Medicine of Fujian Higher Institutions,Fuzhou 350122,China)
出处
《云南中医中药杂志》
2025年第5期79-86,共8页
Yunnan Journal of Traditional Chinese Medicine and Materia Medica
基金
福建省自然科学基金项目(2022J01368)。
关键词
熊果酸
结直肠癌
细胞凋亡
增殖
肿瘤血管新生
炎症
Ursolic Acid
Colorectal Cancer
Apoptosis
Proliferation
Tumor Angiogenesis
Inflammation
作者简介
第一作者:陈洋佚(2000-),女,硕士研究生,研究方向:中西医结合肿瘤研究;通信作者:林久茂,E-mail:linjiumao@fjtcm.edu.cn。
