Article(id=1291707047733653612, tenantId=1146029695717560320, journalId=1246415772164075586, issueId=1291707004800750583, articleNumber=null, orderNo=null, doi=10.13699/j.cnki.1001-6821.2025.22.009, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=1754409600000, receivedDateStr=2025-08-06, revisedDate=null, revisedDateStr=null, acceptedDate=null, acceptedDateStr=null, onlineDate=1785896558936, onlineDateStr=2026-08-05, pubDate=1764259200000, pubDateStr=2025-11-28, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1785896558936, onlineIssueDateStr=2026-08-05, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1785896558936, creator=13701087609, updateTime=1785896558936, updator=13701087609, issue=Issue{id=1291707004800750583, tenantId=1146029695717560320, journalId=1246415772164075586, year='2025', volume='41', issue='22', pageStart='3151', pageEnd='3300', issueExtLink='null', onlineDate='null', pubDate='1764259200000', pubDateStr='2025-11-28', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=null, createTime=1785896548700, creator='13701087609', updateTime=1785896693213, updator='13701087609', preIssue=null, nextIssue=null, articleTotal=null, ext={EN=IssueExt(id=1291707610999316815, tenantId=1146029695717560320, journalId=1246415772164075586, issueId=1291707004800750583, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1291707610999316816, tenantId=1146029695717560320, journalId=1246415772164075586, issueId=1291707004800750583, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null, downloadFileDto=null}, startPage=3206, endPage=3213, ext={EN=ArticleExt(id=1291707048186638445, articleId=1291707047733653612, tenantId=1146029695717560320, journalId=1246415772164075586, language=EN, title=Effects of lycorine on proliferation and apoptosis of acute promyelocytic leukemia cells by regulating PTEN/PI3K/AKT pathway, 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 lycorine (LYC) on the proliferation and apoptosis of acute promyelocytic leukemia (APL) cells by regulating the phosphatase and tensin homolog deleted on chromosome ten (PTEN)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway.
Methods Human APL cells (NB4) were treated with 1.0-32.0 μmol·L-1 LYC, the cell viability was detected, and the LYC experimental concentration was screened. NB4 cells were divided into group A (control group), group B, group C, group D (lycorine low concentration group, medium concentration group, high concentration group), group E (high concentration lycorine+PI3K activator 740 Y-P group). Except for the control group, groups B, C, and D were treated with 4.0, 8.0 and 16.0 μmol·L-1 lycorine, respectively, for 24 hours. Group E was treated with 16.0 μmol·L-1 lycorine combined with 25.0 μmol·L-1 740 Y-P for 24 hours. Cell proliferation, apoptosis, invasion, migration, and cell cycle status were detected, and the expression of related proteins was detected.
Results After treatment with concentrations of 4.0, 8.0 and 16.0 μmol·L-1 of lycorine, the survival rate of NB4 cells prominently decreased, therefore, they were used for subsequent experiments. The colony formation numbers of NB4 cells in group A, group B, group C, group D and group E were 151.38±16.42, 117.15±12.78, 81.04±8.36, 56.17±6.05 and 105.02±10.64, respectively. The scratch healing rates were (89.62±9.15) %, (72.57±7.45)%, (55.34±5.83)%, (36.78±3.72)% and (65.59±6.58)%, respectively. The number of cell invasion was (168.27±17.82), (132.69±14.39), (90.58±9.25), (61.64±6.37) and (110.59±12.27), respectively. The proportion of cells in S phase was (46.17±4.71)%, (35.18±3.56)%, (28.20±3.13)%, (20.52±2.16)% and (32.01±3.32)%, respectively. The percentages of cells in G2/M phase were (24.68±2.56)%, (19.34±1.97)%, (15.62±1.55)%, (11.15±1.23)% and (17.03±1.89)%, respectively. The levels of cyclin dependent kinase 1 (CDK1) were 0.95±0.09, 0.74±0.07, 0.50±0.05, 0.32±0.03 and 0.63±0.06, respectively. The levels of matrix metalloproteinase 2 (MMP-2) were 1.14±0.11, 0.83±0.08, 0.56±0.05, 0.37±0.03 and 0.69±0.06, respectively. The levels of matrix metalloproteinase 9 (MMP-9) were 0.94±0.09, 0.70±0.07, 0.47±0.04, 0.26±0.02 and 0.55±0.05, respectively. The phosphorylated phosphatidylinositol 3-kinase (p-PI3K)/PI3K were 0.86±0.08, 0.71±0.07, 0.45±0.04, 0.26±0.02 and 0.55±0.05, respectively. The expression levels of phosphorylated protein kinase B (p-AKT)/AKT were 0.91±0.09, 0.78±0.07, 0.53±0.05, 0.31±0.03 and 0.69±0.06, respectively. The apoptosis rates were (2.23±0.26)%, (17.41±1.82)%, (26.34±2.75)%, (39.62±4.05)% and (21.58±2.27)%, respectively. The proportion of cells in G0/G1 phase was (29.15±3.06)%, (45.48±4.67)%, (56.18±5.73)%, (68.33±6.88)% and (50.96±5.01)%, respectively. The levels of Bcl-2 associated X protein (Bax) were 0.26±0.02, 0.41±0.04, 0.72±0.07, 0.98±0.09 and 0.66±0.06, respectively. The levels of PTEN were 0.32±0.03, 0.45±0.04, 0.74±0.07, 0.96±0.09 and 0.61±0.06, respectively. Group B, group C, group D compared with group A, group E compared with group D, the above indicators were statistically significant (P<0.05). After NK cells were co-cultured with NB4 cells, compared with the A group, the cell killing rate of B, C and D groups increased (P<0.001). Compared with the D group, the cell killing rate of E group decreased (P<0.001).
Conclusion Lycorine inhibited APL cells with up-regulation of PTEN expression and inhibition of PI3K/AKT pathway, and its effect is dependent on PI3K/AKT pathway.
, authors=Zhen-wei QIN
a, Xin-meng WANG
b, Yin SUN
c, Jing ZHONG
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目的 探究石蒜碱（LYC）调节磷酸酶和张力蛋白同源物（PTEN）/磷脂酰肌醇3激酶（PI3K）/蛋白激酶B（AKT）信号通路对急性早幼粒细胞白血病（APL）细胞增殖及凋亡的影响。
方法 用1.0~32.0 μmol·L-1的石蒜碱处理人APL细胞（NB4）细胞，检测细胞活性，筛选石蒜碱实验浓度；将NB4细胞分为A组（对照组）、B组、C组、D组（石蒜碱低浓度组、中浓度组、高浓度组）、E组（高浓度石蒜碱+PI3K激活剂740 Y-P组），对照组除外，B组、C组、D组分别用石蒜碱4.0、8.0和16.0 μmol·L-1处理24 h；E组用16.0 μmol·L-1石蒜碱和25.0 μmol·L-1的740 Y-P处理24 h；检测细胞增殖、凋亡、侵袭、迁移以及细胞周期情况；检测相关蛋白表达。将人自然杀伤细胞（NK细胞）与NB4细胞共培养24 h，检测NK细胞对NB4细胞的杀伤率。
结果 NB4细胞用石蒜碱4.0、8.0和16.0 μmol·L-1处理后，细胞存活率显著降低，此浓度用于后续实验。A组、B组、C组、D组和E组NB4细胞克隆形成数分别为（151.38±16.42）、（117.15±12.78）、（81.04±8.36）、（56.17±6.05）和（105.02±10.64）个，划痕愈合率分别为（89.62±9.15）%、（72.57±7.45）%、（55.34±5.83）%、（36.78±3.72）%和（65.59±6.58）%，细胞侵袭数量分别为（168.27±17.82）、（132.69±14.39）、（90.58±9.25）、（61.64±6.37）和（110.59±12.27）个，S期细胞比例分别为（46.17±4.71）%、（35.18±3.56）%、（28.20±3.13）%、（20.52±2.16）%和（32.01±3.32）%，G2/M期细胞比例分别为（24.68±2.56）%、（19.34±1.97）%、（15.62±1.55）%、（11.15±1.23）%和（17.03±1.89）%，周期素依赖性激酶1（CDK1）水平分别为0.95±0.09、0.74±0.07、0.50±0.05、0.32±0.03和0.63±0.06，基质金属蛋白酶-2（MMP-2）水平分别为1.14±0.11、0.83±0.08、0.56±0.05、0.37±0.03和0.69±0.06，基质金属蛋白酶-9（MMP-9）水平分别为0.94±0.09、0.70±0.07、0.47±0.04、0.26±0.02和0.55±0.05，磷酸化磷脂酰肌醇3激酶（p-PI3K）/PI3K分别为0.86±0.08、0.71±0.07、0.45±0.04、0.26±0.02和0.55±0.05，磷酸化蛋白激酶B（p-AKT）/AKT表达量分别为0.91±0.09、0.78±0.07、0.53±0.05、0.31±0.03和0.69±0.06，细胞凋亡率分别为（2.23±0.26）%、（17.41±1.82）%、（26.34±2.75）%、（39.62±4.05）%和（21.58±2.27）%，G0/G1期细胞比例分别为（29.15±3.06）%、（45.48±4.67）%、（56.18±5.73）%、（68.33±6.88）%和（50.96±5.01）%，Bcl-2相关X蛋白（Bax）水平分别为0.26±0.02、0.41±0.04、0.72±0.07、0.98±0.09和0.66±0.06，PTEN水平分别为0.32±0.03、0.45±0.04、0.74±0.07、0.96±0.09和0.61±0.06，B组、C组、D组与A组相比，E组与D组相比，以上指标在统计学上差异均有统计学意义（均P<0.05）。NK细胞与NB4细胞共培养后，与A组相比，B组、C组、D组细胞杀伤率升高（P<0.001），与D组相比，E组细胞杀伤率降低（P<0.001）。
结论 石蒜碱抑制APL细胞增殖，促进APL细胞凋亡，并伴随PTEN表达上调和PI3K/AKT通路抑制，且其效应依赖于PI3K/AKT通路。
, authors=秦桢伟
a, 王欣萌
b, 孙寅
c, 钟睛
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