Page 21 - 《中国药房》2024年7期

·药学研究·

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
Δ

＊
刘嘉欣 ，张 韵，黄慧贤，李建芬，姚志新（广州中医药大学第一附属医院/广东省中医临床研究院药学部门诊
中药房，广州 510405）

中图分类号 R965；R734.2 文献标志码 A 文章编号 1001-0408（2024）07-0787-06
DOI 10.6039/j.issn.1001-0408.2024.07.04

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，Western blot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、12 μmol/L；CUR 8
μmol/L+ZER 6 μmol/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。
关键词 姜黄素；花姜酮；非小细胞肺癌；A549细胞；协同作用

Study on the synergistic effect and mechanism of curcumin combined with zerumbone on the biological
behavior of non-small cell lung cancer cells
LIU Jiaxin，ZHANG Yun，HUANG Huixian，LI Jianfen，YAO Zhixin（TCM Pharmacy， Pharmacy Department，
the First Affiliated Hospital of Guangzhou University of Chinese Medicine/Guangdong Clinical Research
Academy of Chinese Medicine， Guangzhou 510405， China）

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.
KEYWORDS curcumin； zerumbone； non-small cell lung cancer； A549 cells； synergistic effect

肺癌，特别是非小细胞肺癌（non-small cell lung
Δ 基金项目 广东省中医药局科研项目（No.20221152）
cancer，NSCLC），在恶性肿瘤领域的发病率和病死率常
＊第一作者 主管中药师。研究方向：医院中药学、临床中药学。
E-mail：26828070@qq.com 年高居榜首。目前，虽然新型药物研发和治疗策略都有

中国药房 2024年第35卷第7期 China Pharmacy 2024 Vol. 35 No. 7 · 787 ·