葛根芩连汤和葛根芩连丸增强伊立替康抗结直肠癌活性的优效性评价  

Evaluation of the efficacy of Gegen Qinlian Decoction and Gegen Qinlian Pills in enhancing the anti-colorectal cancer activity of irinotecan

作　　者：胡丁欣 张颖[1] 张尊建[1] 许风国[1,2] 张培 HU Dingxin;ZHANG Ying;ZHANG Zunjian;XU Fengguo;ZHANG Pei(School of Pharmacy,China Pharmaceutical University,Nanjing 210009,China;School of Traditional Chinese Pharmacy,China Pharmaceutical University,Nanjing 210009,China)

机构地区：[1]中国药科大学药学院,江苏南京210009 [2]中国药科大学中药学院,江苏南京210009

出　　处：《药学研究》2025年第1期1-7,41,共8页Journal of Pharmaceutical Research

基　　金：国家自然科学基金项目(No.82104117、82173947)。

摘　　要：目的评价葛根芩连汤(GQD)和葛根芩连丸(GQP)增强抗结直肠癌(CRC)一线化疗药物伊立替康(CPT-11)活性的优效性。方法以人源CRC细胞系HCT-116为模型,评价GQD、GQP对CPT-11体外抗CRC活性的影响;进一步构建裸鼠皮下移植瘤模型,设置Model组、CPT-11组、GQD组、GQP组、GQD+CPT-11组和GQP+CPT-11组(n=8),评价GQD和GQP的体内抗CRC活性及二者对CPT-11药效的影响。结果体外实验结果表明,GQD能够协同增强CPT-11对肿瘤细胞的抑制作用,而GQP与CPT-11联用表现为加和效应。动物实验结果显示,GQD和GQP均能够增强CPT-11体内抗肿瘤活性,且GQP与CPT-11联用表现为协同效应(金正均Q=1.18)。在此基础上,利用非目标化学物质组学比较了GQD和GQP的成分差异,发现相比于GQD,GQP中苷类成分含量较低,而苷元类成分含量较高,可能与二者体内药效差异有关。结论本研究发现GQD及GQP可增强化疗药物CPT-11的抗CRC活性,且GQP在体内与CPT-11联用表现为更优的协同效应,该研究可为中西药联用治疗CRC提供新的方案。Objective This study aimed to compare the efficacy of Gegen Qinlian Pill(GQP)and Gegen Qinlian Decoction(GQD)in enhancing the activity of Irinotecan(CPT-11)against colorectal cancer(CRC).Methods The in vitro efficacy was first assessed using the human CRC cell line HCT-116.Next,a xenograft mouse model was constructed to evaluate the in vivo anti-CRC efficacy.Mice were randomized into six groups(n=8):Model,CPT-11,GQD,GQP,GQD+CPT-11,and GQP+CPT-11.Results The cell experiments demonstrated that GQD synergistically enhanced the inhibitory effect of CPT-11,while the combination of GQP and CPT-11 showed an additive effect.In vivo,both GQD and GQP significantly enhanced the anti-tumor activity of CPT-11,with GQP exhibiting a synergistic effect,as indicated by a combination index(Q value)of 1.18.To further investigate the underlying mechanisms,we used liquid chromatography-mass spectrometry to compare the chemical component differences between GQD and GQP.The results revealed that GQP was less abundant in glycosides but more abundant in aglycones compared to GQD,which may contribute to the distinct efficacies observed between GQD and GQP in vivo.Conclusion This study confirms that both GQD and GQP can enhance the anti-CRC activity of CPT-11,with GQP demonstrating a synergistic effect in vivo.These results suggest a potential new strategy for combining traditional Chinese medicines and western medicines in CRC treatment.

关 键 词：葛根芩连汤 葛根芩连丸 伊立替康 结直肠癌 药物联用 

分 类 号：R285.5[医药卫生—中药学]