首页|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

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

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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(40 μg/ml β-Ele)、DDP组(2 mg/L DDP)、β-Ele+DDP 组(40 μg/ml β-Ele 联合 2 mg/L DDP)和 β-Ele+DDP+PI3K 激活剂 740Y-P 组(40 µg/ml β-Ele、2 mg/L DDP和50 μg/ml 740Y-P).采用MTT法检测其增殖活力,计算半数抑制浓度(IC50).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IC50为5.53 mg/L,显著高于CAL-27细胞对DDP的IC50(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G0/G1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G0/G1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.
Effects of β-elemene on proliferation and apoptosis of cisplatin-resistant cells in human oral squamous cell carcinoma via PI3K/Akt pathway
Objective To investigate the effect of β-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(40 μg/ml β-Ele),DDP group(2 mg/L DDP),β-Ele+DDP group(40 μg/ml β-Ele combined with 2 mg/L DDP)and β-Ele+DDP+740Y-P group(40μg/ml β-Ele,2 mg/L DDP and 50 μg/ml 740Y-P).MTT assay was used to detect the proliferation activity of the cells,and the half maximal inhibitory concentration(IC50)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 IC50 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 in β-Ele group and DDP group after 72 h.The cells in β-Ele group were arrested at S phase,while the cells in DDP group were arrested at G0/G1 phase(P<0.05).Compared with the DDP group,the cell proliferation activity of the β-Ele+DDP group was further decreased,the cell cycle was arrested at G0/G1 phase,the apoptosis rate was increased,the relative expression of p-PI3K and p-Akt were decreased(P<0.05).Compared with β-Ele+DDP group,the expression of p-PI3K and p-Akt protein,the proliferation activity of CAL-27/DDP cells were increased in β-Ele+DDP+740Y-P group,while the percentage of apoptosis was decreased(P<0.05).Conclusion β-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.

Oral squamous cell carcinomaβ-elemeneCisplatin-resistant cell linesProliferationApoptosis

王海业、麻颖宜

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450052 郑州 郑州大学第一附属医院河南省口腔医院口腔特诊科

450052 郑州大学第一附属医院河南省口腔医院牙周科

口腔鳞状细胞癌 β-榄香烯 顺铂耐药细胞株 增殖 凋亡

2024

临床肿瘤学杂志
解放军第八一医院

临床肿瘤学杂志

CSTPCD
影响因子:1.583
ISSN:1009-0460
年,卷(期):2024.29(5)
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