基于JAK/STAT3通路探讨香草扶正合剂治疗非小细胞肺癌作用机制  

Mechanism of Xiangcao Fuzheng Mixture in the treatment of non-small cell lung cancer based on JAK/STAT3 pathway

作　　者：潘怡宏[1] 王硕 傅华洲[1] PAN Yihong;WANG Shuo;FU Huazhou(Department of Chinese Medicine,Hangzhou First People's Hospital,Hangzhou,Zhejiang 310003,China;Department of Chinese Medicine,Affiliated Xiaoshan Hospital,Hangzhou Normal University,Hangzhou,Zhejiang 311200,China)

机构地区：[1]杭州市第一人民医院中医科,杭州310006 [2]杭州师范大学附属萧山医院中医科,杭州311200

出　　处：《浙江中西医结合杂志》2025年第3期205-210,217,共7页Zhejiang Journal of Integrated Traditional Chinese and Western Medicine

基　　金：杭州市卫生科技计划(重点)项目(No.2018Z02);国家中医药管理局第七批全国老中医药专家学术经验继承工作室建设项目(No.国中医药人教函[2022]76号);浙江省名老中医专家传承工作室建设项目(No.GZS2020029)。

摘　　要：目的基于Janus激酶(JAK)/信号传导与转录激活因子-3(STAT3)通路探讨香草扶正合剂(XCFZ)治疗非小细胞肺癌(NSCLC)的作用及机制。方法C57BL/6小鼠70只,随机抽取8只小鼠作为空白组,其余小鼠建立Lewis肺癌移植瘤模型后,随机分为模型组、XCFZ低剂量组、XCFZ中剂量组、XCFZ高剂量组、顺铂组和XCFZ+顺铂组,每组8只。XCFZ低、中、高剂量组分别以XCFZ9.23、18.46、36.92 g/kg灌胃,每天1次;顺铂组以顺铂3.21 mg/kg腹腔注射,2天1次;XCFZ+顺铂组以顺铂3.21 mg/kg腹腔注射,2天1次,同时以XCFZ 18.46 g/kg灌胃,每天1次;空白组和模型组以ddH2O 0.2 mL灌胃,每天1次;连续给药14 d。称取各组小鼠体质量、瘤质量、去瘤后体质量,计算抑瘤率。肿瘤组织石蜡切片行苏木精-伊红(HE)染色和脱氧核糖核酸转移酶介导的缺口末端标记法(TUNEL)染色,观察病理改变。采用蛋白免疫印迹(Western blot)法检测小鼠肿瘤组织B细胞淋巴瘤-2(Bcl-2)、Bcl-2相关X蛋白(Bax)、JAK2、磷酸化JAK2(p-JAK2)、STAT3、磷酸化STAT3Tyr705位点(p-STAT3 Tyr705)、磷酸化STAT3 Ser727位点(p-STAT3 Ser727)蛋白表达水平,实时荧光定量PCR(RT-qPCR)检测肿瘤组织Bax、Bcl-2、JAK2、STAT3 mRNA表达水平。结果与模型组比较,XCFZ低、中、高剂量组,顺铂组和XCFZ+顺铂组瘤质量[(1.03±0.28)g、(0.73±0.31)g、(1.03±0.13)g、(0.64±0.29)g、(0.62±0.27)g比(1.64±0.26)g,P<0.05]降低,XCFZ中剂量组去瘤后体质量[(21.25±1.39)g比(19.35±1.81)g,P<0.05]升高;XCFZ低、中、高剂量组,顺铂组和XCFZ+顺铂组小鼠肿瘤组织细胞破坏及凋亡现象明显增多,Bax/Bcl-2蛋白比值[(0.25±0.01)、(0.28±0.04)、(0.17±0.01)、(0.26±0.01)、(0.34±0.05)比(0.13±0.02),P<0.05]及mRNA比值[(4.45±0.19)、(5.64±0.19)、(3.66±0.28)、(5.52±0.79)、(5.58±0.38)比(1.17±0.08),P<0.05]升高;p-JAK2/JAK2[(1.23±0.07)、(0.90±0.23)、(1.30±0.09)、(0.69±0.17)、(0.47±0.06)比(1.68±0.06),P<0.05]、p-STAT3 Tyr705/STAT3[(9.58±0.75Objective To investigate the effect and mechanism of Xiangcao Fuzheng Mixture(XCFZ)in the treatment of non-small cell lung cancer(NSCLC)based on JAK/STAT3 pathway.Methods Seventy C57BL/6 mice were used in the study.Eight mice were randomly selected as the blank group,while the remaining mice were used to establish a Lewis lung cancer transplantation tumor model.These tumor-bearing mice were randomly divided into a model group,low-,medium-,and high-dose XCFZ groups,a cisplatin group,and a XCFZ+cisplatin group,with 8 mice in each group.The low,medium,and high-dose XCFZ groups were gavaged by XCFZ at doses of 9.23,18.46,and 36.92 g/kg,respectively,once a day.The cisplatin group was intraperitoneally administered cisplatin at a dose of 3.21 mg/kg,once every 2 days.The XCFZ+cisplatin group was gavaged by XCFZ at a dose of 18.46 g/kg once a day,and intraperitoneally administered cisplatin at a dose of 3.21 mg/kg,once every 2 days.The blank group and the model group were gavaged by 0.2 mL ddH2O,once a day.All treatments were continued for 14 days.The body mass,tumor mass,and body mass after tumor removal were measured,and the tumor inhibition rate was calculated for each group of mice.The pathological changes were observed using hematoxylin-eosin(HE)staining and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling(TUNEL)staining in paraffin-embedded sections of tumor tissue.The protein expression levels of B-cell lymphoma-2(Bcl-2),Bcl-2-associated X protein(Bax),JAK2,phosphorylated JAK2(p-JAK2),STAT3,phosphorylated STAT3 at Tyr705(p-STAT3 Tyr705),and phosphorylated STAT3 at Ser727(p-STAT3 Ser727)in the tumor tissues were detected using Western blotting.The mRNA expression levels of Bax,Bcl-2,JAK2,and STAT3 were detected using real-time quantitative PCR.Results Compared with the model group,the low-,medium-,and high-dose XCFZ groups,cisplatin group,and XCFZ+cisplatin group showed significant decrease in tumor mass[(1.03±0.28),(0.73±0.31),(1.03±0.13),(0.64±0.29),(0.62±0.27)vs.(1.64±0.26)g,P<0.05].Th

关 键 词：小鼠 香草扶正合剂 细梗香草 肺癌 JAK/STAT3通路 凋亡 

分 类 号：R285.5[医药卫生—中药学]