机构地区:[1]陕西中医药大学,陕西咸阳712046 [2]陕西中医药大学附属医院,陕西咸阳712000
出 处:《中国实验方剂学杂志》2024年第16期240-252,共13页Chinese Journal of Experimental Traditional Medical Formulae
基 金:国家自然科学基金项目(82074255)。
摘 要:四君子汤是中医经典名方,由人参、白术、茯苓、甘草配伍而成,具有益气健脾的功效,主治脾胃虚弱证,现代临床上也常用于结直肠癌(CRC)、胃癌等消化道肿瘤的防治。其主要有效成分有人参皂苷Rg_(3)、Rb_(1)、Rh_(1)、Rh_(2)、白术内酯Ⅰ、白术内酯Ⅲ、茯苓酸、甘草酸等。大量临床研究表明四君子汤可以防治癌前病变,联合手术放化疗减毒增效,改善患者生活质量、延长生存期,广泛用于CRC的全程治疗中,但其作用机制尚未被系统阐明。该文通过总结近10年相关文献发现,四君子汤及其有效成分可以通过抑制肠道炎症反应,预防炎癌转化;通过调节蛋白53(p53)、Wnt、核转录因子-κB(NF-κB)等信号通路控制肿瘤生长;通过调控Wnt/β-连环蛋白(β-catenin)、河马(Hippo)等信号通路来抑制肿瘤转移;也能通过负调控蛋白酪氨酸激酶(JAK)/信号传导和转录激活子(STAT)、磷脂酰肌醇3-激酶(PI3K)/蛋白激酶B(Akt)等信号通路抑制肿瘤细胞增殖、侵袭和迁移,通过激活骨髓依赖淋巴细胞瘤-2相关X蛋白(Bax)、胱天蛋白酶-9(Caspase-9)等凋亡蛋白促进凋亡,通过下调耐药基因的表达逆转化疗和靶向耐药;还可以恢复肿瘤微环境中的白细胞分化抗原8^(+)胸腺依赖淋巴细胞(CD8^(+)T cell)、巨噬细胞、自然杀伤细胞的活性来增强抗肿瘤免疫;还能通过上调锌指转录因子4(KLF4)改善体质量减轻、肌肉萎缩等肿瘤恶病质症状,延长荷瘤小鼠的生存期。该文还讨论了目前临床和基础研究方面存在的不足,展望了四君子汤与肠道菌群的相互作用等有前景的研究方向,以期为今后新型高效低毒抗CRC新药研发和临床应用提供参考依据。Si Junzitang is a classic traditional Chinese medicine(TCM)formula consists of Ginseng Radix et Rhizoma,Atractylodis Macrocephalae Rhizoma,Poria,and Glycyrrhizae Radix et Rhizoma.With the effects of tonifying Qi and invigorating spleen,it is mainly used to treat the patients with spleen and stomach deficiency.In modern clinical practice,this prescription is employed in the prevention and treatment of digestive tract tumors,including colorectal cancer(CRC)and gastric cancer.The main active components of Si Junzitang include ginsenosides Rg_(3),Rb_(1),Rh_(1),and Rh_(2),atractylodes lactones Ⅰ and Ⅲ,pachymic acid,and glycyrrhizic acid.Clinical studies have shown that Si Junzitang can prevent and treat precancerous lesions,reduce the toxicity and enhance the efficacy of radiotherapy and chemotherapy,improve the quality of life,and prolong the survival time.Si Junzitang is widely used in the whole treatment course of CRC,while its mechanism remains to be systematically elucidated.This article summarizes relevant articles published in the past 10 years and obtains the following findings.Si Junzitang and its active components can prevent the transformation of inflammation into cancer by inhibiting intestinal inflammation.They can control tumor growth by regulating signaling pathways such as protein 53(p53),Wnt,and nuclear factor-kappa B(NF-κB).They can inhibit tumor metastasis by regulating Wnt/β-catenin and Hippo signaling pathways.In addition,they can inhibit the proliferation,invasion,and migration of tumor cells by negatively regulating the Janus kinase 2/signal transducer and activator of transcription 3(JAK2/STAT3)and phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt)signaling pathways.Meanwhile,they can promote the apoptosis of tumor cells by activating apoptotic proteins such as Bax and Caspase-9 and reverse drug resistance in chemotherapy and targeted therapy by downregulating the expression of drug resistance genes.Si Junzitang and its active components can restore the activities of cluster of diff
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