红花多糖对结直肠癌小鼠肿瘤生长及磷脂酰肌醇3-激酶/蛋白激酶B/雷帕霉素靶蛋白信号通路的影响  

Impacts of safflower polysaccharide on tumor growth and PI3K/Akt/mTOR signal pathway in mice with colorectal cancer

作　　者：王伟[1] 王敏 成敏敏 张婷婷[3] WANG Wei;WANG Min;CHENG Minmin;ZHANG Tingting(Department of Oncology,Shan-dong University of Traditional Chinese Medicine Affiliated Hospital Dongying Hospital(Dongying Traditional Chinese Medicine Hospital),Dongying 257055,Shandong,China;不详)

机构地区：[1]山东中医药大学附属医院东营医院(东营市中医院)肿瘤内科,山东东营257055 [2]东营区人民医院肛肠科,山东东营257000 [3]胜利油田中心医院肿瘤科,山东东营257055

出　　处：《实用医学杂志》2025年第5期670-675,共6页The Journal of Practical Medicine

基　　金：国家自然科学基金资助项目(编号:82205057);山东省医学会临床科研资金--齐鲁专项课题(编号:YXH2022ZX02205)。

摘　　要：目的探讨红花多糖对结直肠癌小鼠肿瘤生长的作用及对磷脂酰肌醇3-激酶(phosphoinositide 3-kinase,PI3K)/蛋白激酶B(protein kinase B,Akt)/雷帕霉素靶蛋白(mammalian target of rapamycin,mTOR)信号通路的影响。方法接种结直肠癌SW480细胞建立结直肠癌肿瘤小鼠模型,将建模成功小鼠分为模型组、红花多糖低剂量组[15 mg/(kg·d)]、红花多糖中剂量组[45 mg/(kg·d)]、红花多糖高剂量组[135 mg/(kg·d)],给药结束后,测定小鼠肿瘤体积、质量和抑瘤率;免疫组化染色法检测增殖细胞核抗原(PCNA)蛋白表达;脱氧核糖核苷酸末端转移酶介导的缺口末端标记法(TUNEL)检测细胞凋亡情况;苏木精伊红(HE)染色观察小鼠肿瘤组织形态;实时荧光定量聚合酶链反应(RT-PCR)法检测各组小鼠肿瘤组织PI3K、Akt、mTOR表达水平;免疫印迹法检测各肿瘤组织c-Myc、Bcl-2关联X蛋白(Bcl-2-associated X protein,Bax)、PI3K/Akt/mTOR通路蛋白表达水平。结果与模型组相比,红花多糖(低、中、高)剂量组小鼠肿瘤质量和肿瘤体积、PI3K、Akt、mTOR mRNA及p-PI3K/PI3K、p-Akt/Akt、p-mTOR/mTOR表达水平、c-Myc蛋白降低,Bax蛋白表达升高(P<0.05),随红花多糖浓度升高,抑瘤率也呈升高趋势(P<0.05)。模型组小鼠肿瘤组织中有较多的PCNA阳性细胞;TUNEL染色阳性细胞(绿色)表达很少,细胞凋亡率较低;肿瘤组织细胞排列紧密,体积较大,分化程度较低;红花多糖各剂量组小鼠肿瘤组织中PCNA表达显著减少,TUNEL染色阳性细胞(绿色)显著增加,细胞凋亡率升高(P<0.05),肿瘤组织细胞排列松散,细胞核皱缩,有较多坏死细胞。结论红花多糖可能通过抑制PI3K/Akt/mTOR信号通路来抑制结直肠癌小鼠肿瘤生长。Objective To investigate the effects of safflower polysaccharide on tumor growth and the Phosphoinositide 3‑kinase(PI3K)/Protein Kinase B(Akt)/Mammalian Target of Rapamycin(mTOR)signaling pathway in colorectal cancer mice.Methods The mouse model of colorectal cancer was established by inoculating SW480 colorectal cancer cells.The successfully modeled mice were divided into five groups:the control group,the low‑dose safflower polysaccharide group 15 mg/(kg·day),the medium‑dose safflower polysaccharide group 45 mg/(kg·day),and the high‑dose safflower polysaccharide group 135 mg/(kg·day).After treatment,tumor volume,mass,and tumor inhibition rate were measured.Immunohistochemistry was used to detect the expression of Proliferating Cell Nuclear Antigen(PCNA)protein.Apoptosis was assessed using the Terminal deoxynucleotidyl Transferase‑Mediated Nick End Labeling(TUNEL)method.Hematoxylin‑Eosin(HE)staining was performed to observe the morphology of tumor tissues.Real‑time polymerase chain reaction(RT‑PCR)was employed to measure the expression levels of PI3K,Akt,and mTOR in tumor tissues from each group.Western blot analysis was conducted to evaluate the expression levels of c‑Myc,Bcl‑2‑associated X protein(Bax),and proteins related to the PI3K/Akt/mTOR pathway.Results Compared with the model group,the safflower polysaccharide(low,medium,and high)dose groups exhibited significantly decreased tumor mass and volume,as well as reduced mRNA levels of PI3K,Akt,and mTOR.Additionally,the expression ratios of p‑PI3K/PI3K,p‑Akt/Akt,p‑mTOR/mTOR,and c‑Myc protein were notably decreased,while the expression of Bax protein was significantly increased(P<0.05).As the concentration of safflower polysaccharide increased,the tumor inhibition rate also increased(P<0.05).In the model group,tumor tissue from mice showed a higher number of PCNA‑positive cells;TUNEL staining revealed minimal green fluorescence,indicating low apoptosis rates.The tumor cells were closely packed,large in size,and poorly differen

关 键 词：红花多糖 结直肠癌 PI3K/Akt/mTOR信号通路 肿瘤生长 增殖细胞核抗原 细胞凋亡 C-MYC Bcl-2关联X蛋白 

分 类 号：R735.3[医药卫生—肿瘤]