首页|藤黄醇提取物对结肠癌干细胞裸鼠原位移植瘤的作用及机制

藤黄醇提取物对结肠癌干细胞裸鼠原位移植瘤的作用及机制

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目的:观察藤黄醇提取物对结肠癌HCT116干细胞裸鼠原位移植瘤的作用及相关作用机制.方法:采用流式细胞术分选和鉴定结肠癌干细胞后,随后建立裸鼠结肠癌干细胞原位移植瘤模型,随机分为5组:G1(空白对照)、G2(5-氟尿嘧啶)、G3(低剂量藤黄醇提取物)、G4(高剂量藤黄醇提取物)、G5(5-氟尿嘧啶和高剂量藤黄醇提取物).通过荧光成像系统观察整体肿瘤发光强度和原位肿瘤发光强度,计算相对肿瘤抑制率和肿瘤延迟时间对药物抗肿瘤疗效进行评估.给药第28天处死裸鼠,记录肿瘤转移的数量和位置.取原发肿瘤病灶称重,并采用Western Blot检测相关蛋白表达.结果:与G1比较,各给药组瘤重和肿瘤荧光强度均有所降低,其中G5相对肿瘤抑制率及肿瘤转移抑制作用最佳.与G1比较,各给药组均显著下调分化抗原簇蛋白44(CD44)、分化抗原簇蛋白133(CD133)、性别决定区Y-box蛋白2(SOX2)、神经性钙黏附蛋白(N-cadherin)和波形蛋白(Vimentin)的表达(P＜0.05,P＜0.01),显著上调上皮性钙黏附蛋白(E-cadherin)的表达(P＜0.01).结论:藤黄醇提取物可能通过抑制结肠癌干细胞调控上皮间质转化过程,发挥抑制结肠肿瘤的增殖、侵袭和转移的作用;且联合5-氟尿嘧啶效果更好.
Effect and mechanism of ethanolic extract of gamboge on colon cancer stem cell orthotopic mouse model
Objective:To investigate the therapeutic effect and mechanism of ethanolic extract of gamboge on colon cancer HCT116 stem cell orthotopic transplanted tumor in nude mice.Methods:Cancer stem cells(CSCs)were sorted and identied by flow cytometry and then the nude mouse colon cancer stem cell orthotopic transplantation tumor model were established.The nude mice were randomly divided into five groups:G1(control),G2(5-fluorouracil),G3 and G4(ethanolic extract of gamboge at low dose and high dose),G5(the 5-fluorouracil+high-dose of ethanolic extract of gamboge).The overall tumor luminescence intensity and in situ tumor luminescence intensity were observed by a fluorescence imaging system,the relative tumor inhibition rate and tumor delay time were calculated to evaluate the anti-tumor efficacy of the drug.Nude mice were sacrificed on the 28th day of administration,and the number and location of tumor metastasis were recorded.The primary tumor lesions were weighed,and the expression of related proteins were detected by Western Blot.Results:Compared with G1,the tumor weight and tumor fluorescence intensity of each treatment group decreased,with G5 having the best relative tumor inhibition rate and tumor metastasis inhibition effect.Compared with Gl,each treatment group significantly downregulated the expression of cluster of differentiated antigen protein 44(CD44),cluster of differentiated antigen protein 133(CD133),sex determining region Y-box protein 2(SOX2),neurogenic calcium adherin(N-cadherin),and vimentin(P＜0.05,P＜0.01),and significantly upregulated the expression of epithelial calcium adherin(E-cadherin)(P＜0.01).Conclusion:The ethanolic extract of gamboge inhibits the colon tumor proliferation,invasion and metastasis of colorectal tumor via regulating EMT process and inhibiting colon cancer stem cells.The treatment of the ethanolic extract of gamboge combined with 5-fluorouracil is better.

GambogeEthanolic extractColon cancer stem cellsEpithelial to mesenchymal transition(EMT)StemnessMechanismColorectal cancer(CRC)5-fluorouracil

李悠然、谷云飞、王微、吴旻娜、贡钰霞、王浩

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南京中医药大学附属医院(江苏省中医院)肛肠外科,南京 210029

南京中医药大学,南京 210046

藤黄 醇提取物 结肠癌干细胞 上皮间质转化 干性 机制 结直肠癌 5-氟尿嘧啶

国家自然科学基金青年科学基金项目江苏省自然科学基金青年基金项目江苏省卫生健康委科技项目江苏省高等学校基础科学面上项目江苏省中医院高峰学术人才项目

81904204BK20191091M202106121KJB360005y2021rc35

2024

中华中医药杂志
中华中医药学会

中华中医药杂志

CSTPCD北大核心
影响因子：1.135
ISSN：1673-1727
年,卷(期)：2024.39(2)
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