Article(id=1291704942339846242, tenantId=1146029695717560320, journalId=1246415772164075586, issueId=1291704771212234905, articleNumber=null, orderNo=null, doi=10.13699/j.cnki.1001-6821.2025.17.010, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=1737302400000, receivedDateStr=2025-01-20, revisedDate=null, revisedDateStr=null, acceptedDate=null, acceptedDateStr=null, onlineDate=1785896056970, onlineDateStr=2026-08-05, pubDate=1758038400000, pubDateStr=2025-09-17, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1785896056970, onlineIssueDateStr=2026-08-05, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1785896056970, creator=13701087609, updateTime=1785896056970, updator=13701087609, issue=Issue{id=1291704771212234905, tenantId=1146029695717560320, journalId=1246415772164075586, year='2025', volume='41', issue='17', pageStart='2401', pageEnd='2550', issueExtLink='null', onlineDate='null', pubDate='1758038400000', pubDateStr='2025-09-17', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=null, createTime=1785896016147, creator='13701087609', updateTime=1785896900366, updator='13701087609', preIssue=null, nextIssue=null, articleTotal=null, ext={EN=IssueExt(id=1291708479866164175, tenantId=1146029695717560320, journalId=1246415772164075586, issueId=1291704771212234905, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1291708479866164176, tenantId=1146029695717560320, journalId=1246415772164075586, issueId=1291704771212234905, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null, downloadFileDto=null}, startPage=2453, endPage=2458, ext={EN=ArticleExt(id=1291704942545367139, articleId=1291704942339846242, tenantId=1146029695717560320, journalId=1246415772164075586, language=EN, title=Reaserch on regulation of baicalein combined with 5-fluorouracil in regulating the malignant biological behavior of small cell lung cancer H446 cells, columnId=1246531407326105792, journalTitle=Chinese Journal of Clinical Pharmacology, columnName=Clinical and Basic Bridging Research, runingTitle=null, highlight=null, articleAbstract=
Objective To investigate the effects of baicalein combined with 5-fluorouracil (5-FU) on the proliferation, apoptosis and migration of H446 cells, and to explore the sensitization mechanism.
Methods Lung cancer H466 cells were allocated into blank, control, experimental and combination groups. The blank group was treated with 10 μmol·L-1 dimethyl sulfoxide, the control group with 20 μmol·L-1 baicalein, the experimental group with 20 μmol·L-1 5-FU, and the combination group with 10 μmol·L-1 baicalein plus 10 μmol·L-1 5-FU. Cell viability was determined using the cell counting kit-8 assay. Apoptosis and reactive oxygen species (ROS) levels were analyzed by flow cytometry. Cell migration was evaluated with Transwell assays, and alterations in mitogen-activated protein kinase (MAPK) pathway protein expression were examined by Western blotting.
Results After 24 h of incubation, cell viability in blank, control, experimental and combination groups were (114.34±2.88)%, (79.87±3.48)%, (57.66±1.82)% and (40.31±2.73)%, respectively; the corresponding apoptosis rates were (14.47±1.36)%, (33.94±4.33)%, (49.20±3.82)% and (49.17±2.13)%; and cell migration rates were (8.43±1.94)%, (11.25±1.55)%, (26.74±3.31)% and (68.83±4.32)%. Compared with control group, the above indexes of experimental group and combined group were significantly increased, and combined group were significantly higher than experimental group (all P<0.01). After adding ROS scavenger NAC to combination group, the apoptosis rates of blank group, control group, experimental group, combination group and combination group+NAC were (7.82±0.94)%, (12.31±2.13)%, (33.48±4.92)%, (52.42±3.17)% and (30.39±2.72)%, respectively; the cell migration rates were (4.36±0.54)%, (4.92±0.71)%, (31.43±3.14)%, (52.64±5.26)% and (27.61±3.52)%, respectively. Compared with combined group, the above indexes of combined group+NAC were significantly decreased (all P<0.01). The relative expression levels of p-JNK protein in blank, experimental, control, combination and combination group+NAC were 0.78±0.05, 0.70±0.04, 0.73±0.03, 0.98±0.02 and 0.73±0.05, respectively; the relative expression levels of p-p38 were 0.56±0.02, 0.51±0.03, 0.60±0.04, 0.76±0.06 and 0.54±0.03, respectively; the relative expression levels of p-ERK were 0.34±0.03, 0.30±0.04, 0.28±0.04, 0.18±0.03 and 0.33±0.05, respectively. The relative expression levels of p-JNK and p-p38 protein in combination group were significantly higher than those in control group, and the relative expression levels of p-ERK protein were significantly lower (all P<0.01); the relative expression levels of p-JNK and p-p38 low protein in combined group+NAC were significantly decreased, while the relative expression levels of p-ERK protein were significantly increased (all P<0.01).
Conclusion The combination of baicalein and 5-FU can enhance the inhibitory effect on proliferation, induce apoptosis, and suppress migration in H446 cells by upregulating ROS levels, activating the JNK and p38 pathways, and inhibiting the ERK pathway.
, authors=Zhi-guang LIU, Xue-zhong WANG, Ya-long DU, authorsList=Zhi-guang LIU, Xue-zhong WANG, Ya-long DU, authorCompany=null, correspAuthors=Zhi-guang LIU, 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=1291704942968991844, articleId=1291704942339846242, tenantId=1146029695717560320, journalId=1246415772164075586, language=CN, title=黄芩素联合5-氟尿嘧啶调控小细胞肺癌H446细胞恶性生物学行为的研究, columnId=1246531407485489349, journalTitle=中国临床药理学杂志, columnName=临床与基础桥接研究, runingTitle=null, highlight=null, articleAbstract=
目的 探索黄芩素联合5-氟尿嘧啶（5-FU）对肺癌H466细胞增殖、凋亡及迁移的影响。
方法 将肺癌H466细胞分成空白组、对照组、实验组和联合组。空白组给予10 mol·L-1的二甲基亚砜；对照组给予20 mol·L-1黄芩素；实验组给予20 mol·L-1 5-FU；联合组给予10 mol·L-1黄芩素+10 mol·L-1 5-FU。用细胞计数试剂盒-8（CCK-8）实验法检测细胞存活率，用流式细胞仪检测细胞凋亡情况和活性氧（ROS）水平，用Transwell法检测细胞迁移情况，用蛋白质印迹法检测丝裂原活化蛋白激酶（MAPK）通路蛋白表达水平变化情况。
结果 空白组、对照组、实验组和联合组24 h后存活率分别为（114.34±2.88）%、（79.87±3.48）%、（57.66±1.82）%和（40.31±2.73）%，细胞凋亡率分别为（14.47±1.36）%、（33.94±4.33）%、（49.20±3.82）%和（49.17±2.13）%，细胞迁移率分别为（8.43±1.94）%、（11.25±1.55）%、（26.74±3.13）%和（68.83±4.32）%，试验组和联合组的上述指标与对照组比较均显著升高，且联合组的上述指标均显著高于试验组（均P<0.01）。在联合组中加入ROS清除剂NAC后，空白组、对照组、实验组、联合组和联合组+NAC的细胞凋亡率分别为（7.82±0.94）%、（12.31±2.13）%、（33.48±4.92）%、（52.42±3.17）%和（30.39±2.72）%；细胞迁移率分别为（4.36±0.54）%、（4.92±0.71）%、（31.43±3.14）%、（52.64±5.26）%和（27.61±3.52）%，联合组+NAC的上述指标与联合组相比均显著降低（均P<0.01）。空白组、实验组、对照组、联合组和联合组+NAC的p-JNK蛋白相对表达水平分别为0.78±0.05、0.70±0.04、0.73±0.03、0.98±0.02和0.73±0.05；p-p38相对表达水平分别为0.56±0.02、0.51±0.03、0.60±0.04、0.76±0.06和0.54±0.03；p-ERK相对表达水平分别为0.34±0.03、0.30±0.04、0.28±0.04、0.18±0.03和0.33±0.05。联合组的p-JNK和p-p38蛋白相对表达水平与对照组比较均显著升高，p-ERK蛋白相对表达水平均显著降低（均P<0.01）；联合组+NAC的p-JNK和p-p38低蛋白相对表达水平均显著降低，p-ERK蛋白相对表达水平显著升高（均P<0.01）。
结论 黄芩素联合5-FU能够通过上调肺癌H446细胞中的ROS水平，激活JNK及p38信号通路，抑制ERK信号通路，进一步增强5-FU对H446细胞的增殖抑制、诱导凋亡及抑制迁移作用。
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刘志广（1983-），男，副主任医师，主要从事胸部肿瘤的相关工作和研究
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