姜黄素联合花姜酮对非小细胞肺癌细胞生物学行为的协同作用及机制研究
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篇名: | 姜黄素联合花姜酮对非小细胞肺癌细胞生物学行为的协同作用及机制研究 |
TITLE: | Study on the synergistic effect and mechanism of curcumin combined with zerumbone on the biological behavior of non-small cell lung cancer cells |
摘要: | 目的 研究姜黄素(CUR)联合花姜酮(ZER)对人非小细胞肺癌(NSCLC)A549细胞生物学行为的协同作用及机制。方法采用CCK-8法和金氏公式筛选CUR和ZER联用后协同作用最佳的浓度组合。后续实验分为空白组、CUR组、ZER组和CUR+ZER组,采用流式细胞术评价细胞凋亡情况,克隆形成实验评价细胞增殖能力,划痕实验、Transwell迁移实验评价细胞迁移能力,Transwell侵袭实验评价细胞侵袭能力,Westernblot法检测磷酸化磷脂酰肌醇-3-激酶(p-PI3K)、磷酸化蛋白激酶B(p-Akt)、血管内皮生长因子A(VEGF-A)蛋白的相对表达水平。结果CUR、ZER对A549细胞的半数抑制浓度约为16、12μmol/L;CUR8μmol/L+ZER6μmol/L组合的药物联用增效指数最大,其细胞增殖抑制率为(77.41±4.16)%,协同作用最明显。与CUR组、ZER组比较,CUR+ZER组细胞凋亡率显著升高(P<0.01),细胞克隆形成率、细胞迁移率、迁移细胞数、侵袭细胞数,以及细胞中p-PI3K、p-Akt、VEGF-A蛋白的相对表达水平均显著降低(P<0.05或P<0.01)。结论CUR和ZER联用后起到协同作用,能显著促进NSCLC细胞凋亡,抑制细胞增殖、迁移和侵袭,其潜在机制可能与抑制PI3K/Akt信号通路,进而下调VEGF-A的蛋白表达密切相关。 |
ABSTRACT: | OBJECTIVE To investigate the synergistic effect and mechanism of curcumin (CUR) combined with zerumbone (ZER) on the biological behavior of non-small cell lung cancer (NSCLC) A549 cells. METHODS CCK-8 method and Gin’s formula were used to screen the optimal concentration combination for synergistic effect after the combination of CUR and ZER. The cells were divided into blank group, CUR group, ZER group, and CUR+ZER group. Flow cytometry was used to evaluate cell apoptosis, and clone formation experiment was used to evaluate cell proliferation ability, scratch experiment and Transwell migration experiment were used to evaluate cell migration ability, and Transwell invasion experiment was used to evaluate cell invasion ability. Western blot assay was used to detect the protein expressions of phosphorylated phosphatidylinositol-3-kinase (p- PI3K), phosphorylated protein kinase B (p-Akt), and vascular endothelial growth factor A (VEGF-A). RESULTS The half inhibitory concentrations of CUR and ZER on A549 cells were approximately 16 and 12 μmol/L, respectively; the drug combination of CUR 8 μmol/L+ZER 6 μmol/L had the highest efficiency enhancement index, with the cell proliferation inhibition rate of (77.41±4.16)%, indicating the most significant synergistic effect. Compared with the CUR and ZER groups, the cell apoptosis rate in the CUR+ZER group was significantly increased (P<0.01), while the cell clone formation rate, cell migration rate, the number of migrating cells, the number of invading cells, and relative expression levels of p-PI3K, p-Akt, and VEGF-A proteins in the cells were significantly reduced (P<0.05 or P<0.01). CONCLUSIONS The combination of CUR and ZER has a synergistic effect, significantly promoting the apoptosis of NSCLC cells, and inhibiting cell proliferation, migration, and invasion. Its potential mechanism may be closely related to the inhibition of the PI3K/Akt signaling pathway, thereby down-regulating the protein expression of VEGF-A. |
期刊: | 2024年第35卷第07期 |
作者: | 刘嘉欣;张韵;黄慧贤;李建芬;姚志新 |
AUTHORS: | LIU Jiaxin,ZHANG Yun,HUANG Huixian,LI Jianfen,YAO Zhixin |
关键字: | 姜黄素;花姜酮;非小细胞肺癌;A549细胞;协同作用 |
KEYWORDS: | curcumin; zerumbone; non-small cell lung cancer; A549 cells; synergistic effect |
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