中药新药与临床药理2026，Vol.37Issue(1)：42-51,10.DOI:10.19378/j.issn.1003-9783.2026.01.005
正得康诱导肺癌细胞凋亡及抑制肺癌转移的线粒体通路机制
Mechanism of Zhengdekang in Inducing Apoptosis and Inhibiting Metastasis of Lung Cancer Cells via the Mitochondrial Pathway
摘要
Abstract
Objective To investigate the effect and mechanism of the Chinese herbal compound Zhengdekang(ZDK)in inhibiting lung cancer metastasis.Methods In vitro,CCK-8 assay,plate colony formation assay,Transwell migration assay,and flow cytometric apoptosis assay were used to evaluate the effects of ZDK on the proliferation,migration,and apoptosis of human lung adenocarcinoma circulating tumor cells(CTC-TJH-01)and mouse Lewis lung carcinoma(LLC)cells.JC-10 mitochondrial membrane potential staining was employed to assess the effect of ZDK on the mitochondrial membrane potential in CTC-TJH-01 and LLC cells.Western Blot was performed to detect the expression levels of mitochondrial/cytochrome C pathway-related proteins,including Bcl-2,Bax,Cytochrome C,Caspase-9,and Cleaved-Caspase-3,in lung cancer cells after ZDK intervention.In vivo,a lung metastasis model was established in C57BL/6J mice via tail vein injection of LLC cells.The mice were administered ZDK by gavage once daily for 25 days.Lung metastases were observed and photographed after sample collection.Pathological changes in lung tissue were examined by HE staining,and the expression levels of Ki-67 and Cleaved-Caspase-3 proteins in lung metastatic tissues were detected by immunohistochemistry.Results ZDK significantly inhibited the proliferation and migration of CTC-TJH-01 and LLC cells(P＜0.05,P＜0.01,P＜0.001)and markedly induced apoptosis in lung cancer cells(P＜0.001).With increasing concentrations of ZDK,the mitochondrial membrane potential in CTC-TJH-01 and LLC cells gradually decreased(P＜0.01,P＜0.001).ZDK intervention also downregulated the expression of Bcl-2 protein(P＜0.05)and upregulated the expression of Bax,Cytochrome C,Caspase-9,and Cleaved-Caspase-3 proteins in CTC-TJH-01 and LLC cells(P＜0.05,P＜0.01,P＜0.001).In vivo studies showed that ZDK administration significantly reduced the number of lung metastatic nodules in mice(P＜0.01),downregulated the expression of Ki-67 protein(P＜0.001),and upregulated the expression of Cleaved-Caspase-3 protein in lung metastatic tissues(P＜0.001).Conclusion ZDK inhibits lung cancer metastasis by inducing apoptosis in lung cancer cells through regulation of the endogenous mitochondrial apoptotic pathway.关键词
正得康/肺癌/细胞凋亡/线粒体/转移/人肺腺癌循环肿瘤细胞/小鼠Lewis肺癌细胞/小鼠Key words
Zhengdekang/lung cancer/apoptosis/mitochondria/metastasis/human lung adenocarcinoma circulating tumor cells/mouse Lewis lung carcinoma cells/mice分类
医药卫生引用本文复制引用
刘诗卉,李佳轩,田建辉,刘佳君,张志鹏,阙祖俊..正得康诱导肺癌细胞凋亡及抑制肺癌转移的线粒体通路机制[J].中药新药与临床药理,2026,37(1):42-51,10.基金项目
国家自然科学基金面上项目(82174245) （82174245）
上海市炎癌转化病证生物学前沿研究基地(2021KJ03-12) （2021KJ03-12）
上海市卫生健康领军人才(2022LJ014). （2022LJ014）
