β-榄香烯通过PI3K/Akt通路对人口腔鳞癌顺铂耐药细胞增殖和凋亡的影响  

Effects ofβ-elemene on proliferation and apoptosis of cisplatin-resistant cells in human oral squamous cell carcinoma via PI3K/Akt pathway

作　　者：王海业 麻颖宜 WANG Haiye;MA Yingyi(Department of Oral Special Diagnosis,The First Affiliated Hospital of Zhengzhou University,Henan Province Stomatological Hospital,Zhengzhou 450052,China)

机构地区：[1]郑州大学第一附属医院、河南省口腔医院口腔特诊科,郑州450052 [2]郑州大学第一附属医院、河南省口腔医院牙周科,450052

出　　处：《临床肿瘤学杂志》2024年第5期424-429,共6页Chinese Clinical Oncology

摘　　要：目的探讨β-榄香烯(β-Ele)通过PI3K/Akt通路对人口腔鳞癌顺铂(DDP)耐药细胞的增殖、凋亡及耐药性的影响及机制。方法构建DDP耐药细胞株CAL-27/DDP,将细胞分为对照组、β-Ele组(40μg/mlβ-Ele)、DDP组(2 mg/L DDP)、β-Ele+DDP组(40μg/mlβ-Ele联合2 mg/L DDP)和β-Ele+DDP+PI3K激活剂740Y-P组(40μg/mlβ-Ele、2 mg/L DDP和50μg/ml 740Y-P)。采用MTT法检测其增殖活力,计算半数抑制浓度(IC_(50))。流式细胞术检测各组细胞的周期变化及凋亡情况。Western blotting检测PI3K/Akt通路相关蛋白的表达。结果CAL-27/DDP细胞对DDP的IC_(50)为5.53 mg/L,显著高于CAL-27细胞对DDP的IC_(50)(1.45 mg/L)。与对照组比较,β-Ele组和DDP组CAL-27/DDP细胞在72 h的增殖活力降低、凋亡率升高,而p-PI3K和p-Akt相对表达水平降低,其中β-Ele组细胞发生S期阻滞,而DDP组细胞发生G_(0)/G_(1)期阻滞(P<0.05)。与DDP组比较,β-Ele+DDP组细胞增殖活力进一步降低,细胞发生G_(0)/G_(1)期阻滞,凋亡率升高,p-PI3K和p-Akt相对表达水平降低(P<0.05)。与β-Ele+DDP组比较,β-Ele+DDP+740Y-P组的p-PI3K和p-Akt蛋白表达水平升高,CAL-27/DDP细胞增殖率升高,细胞凋亡率降低(P<0.05)。结论β-Ele通过抑制PI3K/Akt信号通路的激活,抑制CAL-27/DDP细胞的增殖活力,促进其凋亡,从而降低其对DDP的耐药性。Objective To investigate the effect ofβ-elemene(β-Ele)on the proliferation,apoptosis and drug resistance of cisplatinum(DDP)resistant human oral squamous cell carcinoma through PI3K/Akt pathway and its mechanism.Methods The cisplatin-resistant cell line CAL-27/DDP was constructed.The cells were divided into control group,β-Ele group(40μg/mlβ-Ele),DDP group(2 mg/L DDP),β-Ele+DDP group(40μg/mlβ-Ele combined with 2 mg/L DDP)andβ-Ele+DDP+740Y-P group(40μg/mlβ-Ele,2 mg/L DDP and 50μg/ml 740Y-P).MTT assay was used to detect the proliferation activity of the cells,and the half maximal inhibitory concentration(IC_(50))was calculated.Flow cytometry to detect cell cycle and apoptosis.Western blotting was used to detect the expression of PI3K/Akt pathway-related proteins.Results IC_(50)of CAL-27/DDP cells to DPP was 5.53 mg/L,which was significantly higher than that of CAL-27 cells to DPP(1.45 mg/L).Compared with the control group,the proliferation activity of CAL-27/DDP cells was decreased,the apoptosis rate was increased,and the relative expression of p-PI3K and p-Akt were decreased inβ-Ele group and DDP group after 72 h.The cells inβ-Ele group were arrested at S phase,while the cells in DDP group were arrested at G_(0)/G_(1)phase(P<0.05).Compared with the DDP group,the cell proliferation activity of theβ-Ele+DDP group was further decreased,the cell cycle was arrested at G_(0)/G_(1)phase,the apoptosis rate was increased,the relative expression of p-PI3K and p-Akt were decreased(P<0.05).Compared withβ-Ele+DDP group,the expression of p-PI3K and p-Akt protein,the proliferation activity of CAL-27/DDP cells were increased inβ-Ele+DDP+740Y-P group,while the percentage of apoptosis was decreased(P<0.05).Conclusionβ-Ele inhibits the proliferation and promotes apoptosis of CAL-27/DDP cells by inhibiting the activation of the PI3K/Akt signaling pathway,thereby reducing the resistance of CAL-27/DDP cells to DDP.

关 键 词：口腔鳞状细胞癌 Β-榄香烯 顺铂耐药细胞株 增殖 凋亡 

分 类 号：R739.8[医药卫生—肿瘤]