现代中西医结合杂志2025，Vol.34Issue(12)：1632-1639,8.DOI:10.3969/j.issn.1008-8849.2025.12.005
白头翁汤联合5-氟尿嘧啶及卡瑞利珠单抗对结肠癌小鼠的抗肿瘤效果和肿瘤免疫微环境的影响研究
Efficacy of Pulsatilla Decoction combined with 5-Fu and camrelizumab on colorectal cancer in mice and its effect on tumor immune microenvironment
摘要
Abstract
Objective It is to explore the anti-tumor effect of Pulsatilla Decoction combined with 5-fluorouracil(5-Fu)and the immune checkpoint inhibitor camrelizumab in mice with colorectal cancer and its effect on tumor immune microenvi-ronment.Methods Forty-eight BALB/c mice were used to establish models of CT26 colon cancer subcutaneous transplanta-tion tumor,and then the modeled mice were randomly divided into model group,5-Fu group,5-Fu+Pulsatilla Decoction group and 5-Fu+Pulsatilla Decoction+camrelizumab group,with 12 mice in each group.The model group was given nor-mal saline by gavage,the 5-Fu group was given 5-Fu 15 mg/kg by intraperitoneal injection,the 5-Fu+Pulsatilla Decoction group was given 5-Fu 15 mg/kg by intraperitoneal injection and Pulsatilla Decoction 7.5 g/kg by gavage,all once daily,totally treated for days;the 5-Fu+Pulsatilla Decoction+camrelizumab group was given canelizumab 30 mg/kg by intraper-itoneal injection once every other day on the treatment of 5-Fu+Pulsatilla Decoction group,totally treated for 18 days.The changes of body weight and tumor volume of mice were observed;the mice were imaged in vivo at the end of the experiment and the total flux and average radiance were calculated;the tumors,thymus and spleen of the mice were extracted and tumor inhibiting rate,thymus index and spleen index were calculated;the pathological morphology of tumor tissues was ob-served by HE staining;the serum levels of interleukin(IL)-2,IL-6,IL-17A and transforming growth factor-β1(TGF-β1)were measured by ELISA;the proportions of CD3+,CD4+,regulatory T cells(Treg),and IL-17A cells in tumor tissues and spleen tissues were detected by flow cytometry;the protein expressions of programmed cell death protein-1(PD-1)and programmed cell death ligand 1(PD-L1)in tumor tissues were detected by Western blot.Results Compared with the mod-el group at the end of the treatment,the body weight,tumor volume,and spleen index of mice were all significantly de-creased in each treatment group(all P<0.05);the tumor cells were degenerated and atrophied to different degrees;the proportion of Treg cells in tumor tissues and spleen tissues,and the relative expressions of PD-1 and PD-L1 proteins in tumor tissues were all significantly decreased(all P<0.05)),and the proportions of CD3+and CD4+cells in tumor tis-sues were significantly increased(both P<0.05);the total flux of mice in the5-Fu+Pulsatilla Decoction group and total flux and average radiance of mouse imaging of mice in the 5-Fu+Pulsatilla Decoction+camrelizumab group were signifi-cantly decreased(all P<0.05);the thymus index,serum level of IL-6 and the proportions of CD3+,CD4+and IL-17A cells in spleen tissues in the5-Fu+Pulsatilla Decoction+camrelizumab group,and the serum level of IL-2 and the pro-portions of CD4+and IL-17A cells in spleen tissues in 5-Fu+Pulsatilla Decoction group were all significantly increased(all P<0.05).The tumor inhibiting rate,thymus index,and the proportion of CD3+cells in tumor tissues were signifi-cantly higher,while the proportion of Treg cells in spleen tissues and the relative protein expressions of PD-1 and PD-L1 in tumor tissues were significantly lower in the 5-Fu+Pulsatilla Decoction group than those in the 5-Fu group(all P<0.05).The tumor inhibiting rate,thymus index,serum level of IL-6 and the proportion of Treg cells in spleen tissues were signifi-cantly higher,while the proportion of Treg cells in tumor tissues and the relative protein expressions of PD-1 and PD-L1 in tumor tissues were significantly lower in the 5-Fu+Pulsatilla Decoction+camrelizumab group than those in the 5-Fu group(all P<0.05);the tumor inhibiting rate,thymus index and serum level of IL-6 were significantly higher,while the serum level of TGF-β1 and the proportions of Treg cells in tumor tissues and the relative protien expressions of PD-1 and PD-L1 in tumor tissues were significantly lower in the 5-Fu+Pulsatilla Decoction+camrelizumab group than those in the 5-Fu+Pul-satilla Decoction group(all P<0.05).Conclusion Pulsatilla Decoction combined with 5-Fu can significantly improve the tumor immune microenvironment and alleviate the inflammatory response in mice with colorectal cancer,thus to enhance the antitumor activity,and the efficacy is more advantageous when combining with camrelizumab.关键词
白头翁汤/氟尿嘧啶/结直肠癌/免疫调节Key words
Pulsatilla Decoction/fluorouracil/colorectal cancer/immune regulation分类
医药卫生引用本文复制引用
陈治宇,马琪琪,塔吉姑丽·吐逊,节阳华..白头翁汤联合5-氟尿嘧啶及卡瑞利珠单抗对结肠癌小鼠的抗肿瘤效果和肿瘤免疫微环境的影响研究[J].现代中西医结合杂志,2025,34(12):1632-1639,8.基金项目
新疆维吾尔自治区自然科学基金面上项目(2022D01C560) （2022D01C560）
"天山英才"医药卫生高层次人才培养计划项目(TSYC202301B080) （TSYC202301B080）
