Article(id=1317115040600273219, tenantId=1146029695717560320, journalId=1255847919539208197, issueId=1317114999827452826, articleNumber=null, orderNo=null, doi=10.13193/j.issn.1673-7717.2026.06.026, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=null, receivedDateStr=null, revisedDate=null, revisedDateStr=null, acceptedDate=null, acceptedDateStr=null, onlineDate=1791954296492, onlineDateStr=2026-10-14, pubDate=1781020800000, pubDateStr=2026-06-10, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1791954296492, onlineIssueDateStr=2026-10-14, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1791954296492, creator=13701087609, updateTime=1791954296492, updator=13701087609, issue=Issue{id=1317114999827452826, tenantId=1146029695717560320, journalId=1255847919539208197, year='2026', volume='44', issue='6', pageStart='1', pageEnd='258', issueExtLink='null', onlineDate='null', pubDate='1781020800000', pubDateStr='2026-06-10', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=null, createTime=1791954286772, creator='13701087609', updateTime=1791958677365, updator='13701087609', preIssue=null, nextIssue=null, articleTotal=null, ext={EN=IssueExt(id=1317133415753831385, tenantId=1146029695717560320, journalId=1255847919539208197, issueId=1317114999827452826, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1317133415753831386, tenantId=1146029695717560320, journalId=1255847919539208197, issueId=1317114999827452826, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null, downloadFileDto=null}, startPage=146, endPage=151, ext={EN=ArticleExt(id=1317115040847737156, articleId=1317115040600273219, tenantId=1146029695717560320, journalId=1255847919539208197, language=EN, title=Exploring Molecular Mechanism of Liujunzi Decoction (六君子汤) Promoting Apoptosis of Esophageal Cancer-Related Fibroblasts Based on TGF-β1/Smad2 Pathway, columnId=1256183361521967297, journalTitle=Chinese Archives of Traditional Chinese Medicine, columnName=Target on National Project, runingTitle=null, highlight=null, articleAbstract=
Objective Cancer-associated fibroblasts (CAFs), which have the properties of myofibroblasts, are fibroblasts in tumor tissue that are activated by cancer cells and. CAFs can provide nutritional support and invasion channels for tumor cells, thereby helping tumor cell proliferation, invasion and metastasis. This paper observed the effect of Liujunzi Decoction (六君子汤) on the apoptosis of esophageal cancer-related CAFs and discussed its molecular mechanism, so as to provide experimental basis for the clinical application of Liujunzi Decoction in the treatment of esophageal cancer.
Methods ①The effect of TE-1 conditioned medium (TE-1M) on CAFs activity was detected by MTT method. ②The effect of Liujunzi Decoction on CAFs activity was detected by MTT method. ③The effects of Liujunzi Decoction on the secretion of transforming growth factor-β1 (TGF-β1) from CAFs were measured by ELISA. ④Flow cytometry was performed to detect the effect of Liujunzi Decoction on apoptosis of CAFs. ⑤The effects of Liujunzi Decoction on mRNA expression levels of CAFs apoptosis-related molecules were detected by RT-qPCR.6. The effects of Liujunzi Decoction on apoptosis-related molecular protein expression levels of CAFs were detected by Western Blot.
Results ①The results of MTT showed that compared with the blank group, 50 μg/mL Liujunzi Decoction had no significant effect on the activity inhibition of CAFs, and the other concentration groups had an inhibitory effect on the activity of CAFs (P<0.05). ②The results of MTT showed that compared with the blank group, 10%, 20% and 30% TE-1M had a promoting effect on the proliferation of CAFs, among which 20% TE-1M had the most significant proliferation effect on CAFs (P<0.001), and 40% TE-1M (P<0.05) and 50% TE-1M (P<0.01) had a significant inhibitory effect on the proliferation of CAFs. ③The results of ELISA method showed that compared with the blank group, the content of TGF-β1 secreted by CAFs in the model group decreased (P<0.001), the content of TGF-β1 in the Liujunzi Decoction group was significantly increased (P<0.001), and the content of TGF-β1 in the SB-431542 inhibitor+Liujunzi Decoction group was decreased compared with that in the Liujunzi Decoction group (P<0.001). ④The results of flow cytometry showed that there was no significant difference in the apoptosis rate in the model group compared with that in the blank group. Compared with the model group, the apoptosis rate of the Liujunzi Decoction group was significantly increased (P<0.001), and the apoptosis rate of the SB-431542 inhibitor+Liujunzi Decoction group was significantly decreased compared with the Liujunzi Decoction group (P<0.001). ⑤The results of PCR showed that the expressions of Smad2 and FAP genes in the model group were increased (P<0.01, P<0.001) compared with those in the blank group, and the expressions of Smad2, Caspase-3 and FAP in the Liujunzi Decoction group were significantly increased (P<0.05, P<0.01, P<0.001) compared with those in the model group. Compared with those of the Liujunzi Decoction group, the expressions of Smad2, Caspase-3 and FAP in the were significantly decreased (P<0.05, P<0.001). ⑥The results of Western blot showed that compared with the blank group, the expression of Smad2 protein in the model group decreased (P<0.01). The expressions of Smad2 and Caspase-3 in the Liujunzi Decoction group were significantly increased (P<0.001) compared with those in the model group and the expression level of FAP protein was increased (P<0.05). Compared with those in the Liujunzi Decoction group, the expressions of Smad2 and Caspase-3 were significantly decreased in the SB-431542 inhibitor+Liujunzi Decoction group (P<0.01), and the expression of FAP protein was decreased (P<0.05).
Conclusion The proliferation of CAFs was promoted by inhibiting TGF-β1/Smad2 pathway in indirect coculture with esophageal cancer cells. Liujunzi Decoction can induce CAFs apoptosis through TGF-β1/Smad2 pathway, and the induction effect of TGF-β1/Smad2 pathway on apoptosis of CAFs is more obvious in co-culture environment.
, authors=Yaru LIU
1, Yang LIU
1, Xing CHEN
1, Jianing JIAN
1, Xiaoqiao XIAO
1, Zhexu ZHOU
1, Xiaobo HU
1, Yulong CHEN
2, authorsList=Yaru LIU, Yang LIU, Xing CHEN, Jianing JIAN, Xiaoqiao XIAO, Zhexu ZHOU, Xiaobo HU, Yulong CHEN, authorCompany=null, correspAuthors=Yulong CHEN, authorNote=null, correspAuthorsNote=null, copyrightStatement=null, copyrightOwner=null, extLink=null, articleAbsUrl=null, sourceXml=null, magXml=null, pdfUrl=null, pdf=null, pdfFileSize=null, pdfExtLink=null, richHtmlUrl=null, mobilePdfUrl=null, reviewReport=null, pdfFirstPage=null, abstractGraph=null, abstractGraphContent=null, abstractVideo=null, citation=null, cebUrl=null, magXmlContent=null, mapNumber=null, fund=null), CN=ArticleExt(id=1317115041183281477, articleId=1317115040600273219, tenantId=1146029695717560320, journalId=1255847919539208197, language=CN, title=基于TGF-β1/Smad2通路探讨六君子汤促进食管癌相关成纤维细胞凋亡的分子机制, columnId=1256183362172142382, journalTitle=中华中医药学刊, columnName=国家项目点击, runingTitle=null, highlight=null, articleAbstract=
目的 肿瘤相关成纤维细胞（cancer-associated fibroblasts，CAFs）是肿瘤组织中被癌细胞激活的成纤维细胞，具有成肌纤维细胞的特性。CAFs可以为肿瘤细胞提供营养支持和侵袭通道，从而帮助肿瘤细胞的增殖、侵袭和转移。观察六君子汤对食管癌相关CAFs凋亡的影响，并探讨其分子机制，为六君子汤治疗食管癌的临床应用提供实验依据。
方法 ①MTT法检测不同浓度六君子汤对CAFs活性的影响。②MTT法检测不同浓度TE-1条件培养基（即TE-1M）对CAFs活性的影响。③ELISA检测六君子汤对各分组CAFs分泌转化生长因子-β1（TGF-β1）的影响。④流式细胞术检测各分组CAFs凋亡水平。⑤RT-qPCR检测六君子汤对各分组CAFs凋亡相关分子mRNA的表达水平的影响。⑥Western Blot法检测六君子汤对各分组CAFs凋亡相关分子蛋白的表达水平的影响。
结果 ①MTT检测结果显示：与空白组相比，50 μg/mL的六君子汤对CAFs的活性抑制无明显影响，其他浓度组对CAFs的活性均有抑制作用（P<0.05）。②MTT检测结果显示：与空白组相比，10%、20%和30%TE-1M对CAFs的增殖具有促进作用，其中20%浓度的TE-1M对CAFs的增殖作用最显著（P<0.001），40%TE-1M（P<0.05）及50%TE-1M（P<0.01）对CAFs的增殖有明显的抑制作用。③ELISA法检测结果显示：与空白组相比，模型组CAFs分泌TGF-β1含量下降（P<0.001）；与模型组相比，六君子汤组TGF-β1含量显著升高（P<0.001）；与六君子汤组相比，抑-六君子汤组（SB-431542抑制剂+六君子汤组）TGF-β1含量降低（P<0.001）。④流式细胞术检测结果显示：与空白组相比，模型组凋亡率无明显差异；与模型组相比，六君子汤组凋亡率显著升高（P<0.001）；与六君子汤组相比，抑-六君子汤组凋亡率明显下降（P<0.001）。⑤PCR检测结果显示：与空白组相比，模型组Smad2、FAP基因表达升高（P<0.01，P<0.001）；与模型组相比，六君子汤组Smad2、Caspase-3和FAP表达显著升高（P<0.05，P<0.01，P<0.001）；与六君子汤组相比，抑-六君子汤组Smad2、Caspase-3和FAP明显下降（P<0.05，P<0.001）。⑥Western Blot检测结果显示：与空白组相比，模型组Smad2蛋白表达水平下降（P<0.01）；与模型组相比，六君子汤组Smad2和Caspase-3表达显著升高（P<0.001），FAP蛋白表达水平升高（P<0.05）。与六君子汤组相比，抑-六君子汤组Smad2、Caspase-3明显下降（P<0.01），FAP蛋白表达下降（P<0.05）。
结论 与食管癌细胞间接共培养条件下通过抑制TGF-β1/Smad2通路促进CAFs增殖；六君子汤可以通过TGF-β1/Smad2通路诱导CAFs凋亡。
, authors=刘娅茹
1, 刘洋
1, 陈星
1, 菅佳宁
1, 肖小乔
1, 周哲旭
1, 胡啸博
1, 陈玉龙
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刘娅茹（1997-），女，河南周口人，硕士，研究方向：中医方证信号传导。
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