南方医科大学学报

南方医科大学学报 ›› 2023, Vol. 43 ›› Issue (1): 111-116.doi: 10.12122/j.issn.1673-4254.2023.01.15

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甘草查尔酮A通过调控PI3K/AKT信号通路诱导肺鳞癌细胞周期阻滞

范晓丽，王 娟，王梨明   

  1. 桂林医学院药学院，广西 桂林 541100；桂林医学院临床学院，广西 桂林 541001
  • 出版日期:2023-01-20 发布日期:2023-02-22

Licochalcone A induces cell cycle arrest in human lung squamous carcinoma cells via the PI3K/Akt signaling pathway

FAN Xiaoli, WANG Juan, WANG Liming   

  1. College of Pharmacy, Guilin Medical University, Guilin 541100, China; College of Clinical Medicine, Guilin Medical University, Guilin 541001, China
  • Online:2023-01-20 Published:2023-02-22

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摘要： 目的 探究甘草查尔酮A（LCA）对肺鳞癌细胞增殖和周期的影响及相关分子机制。方法 通过MTT实验检测不同浓度LCA处理48 h对H226细胞增殖的影响并计算半数抑制浓度（IC50）；不同浓度LCA（0、10、20及40 μmol/L）处理H226细胞48 h，通过流式细胞术检测LCA对细胞周期的影响，通过Western blot检测LCA对细胞周期相关蛋白CyclinD1，以及细胞周期蛋白依赖性激酶CDK2和CDK4表达的影响，并探究PI3K/Akt信号通路相关蛋白的表达情况；选取雄性BALB/c-nu裸鼠构建皮下移植瘤模型，随机分为两组（对照组和LCA处理组），腹腔注射LCA 24 d后取肿瘤测量瘤体体积及质量，从体内水平探究LCA的抗肿瘤作用。结果 MTT实验结果表明，与空白组比较，随着LCA浓度的增加，细胞存活率明显降低，48 h的IC50为28.3 μmol/L；流式细胞术的结果表明LCA处理可以使细胞周期阻滞在G1期（P<0.05），Western blot的结果显示，LCA处理后，CyclinD1、CDK2和CDK4的表达均降低（P<0.05）；PI3K和Akt的表达无明显变化，但是它们的磷酸化水平（p-PI3K和p-Akt的表达）显著降低（P<0.05）；裸鼠荷瘤实验表明，LCA可使肿瘤体积和质量明显减小（P<0.05）。结论 LCA可以抑制肺鳞癌的增殖并诱导细胞周期阻滞，其作用机制可能与调控PI3K/AKT信号通路有关。

关键词: 甘草查尔酮A；细胞增殖；细胞周期；PI3K/AKT信号通路

Abstract: Objective To investigate the effect of licochalcone A (LCA) on the proliferation and cell cycle of human lung squamous carcinoma cells and explore its possible molecular mechanism. Methods MTT assay was used to detect the changes in proliferation of H226 cells after treatment with different concentrations of LCA for 48 h, and the IC50 of LCA was calculated. Flow cytometry was used to analyze cell cycle changes in H226 cells treated with 10, 20, and 40 μmol/L LCA, and the expressions of cyclin D1, cyclin-dependent kinase CDK2 and CDK4, and p-PI3K, PI3K, p-Akt, and Akt in the treated cells were detected using Western blotting. The effect of intraperitoneal injection of LCA for 24 days on tumor volume and weight was assessed in a BALB/c-nu mouse model bearing lung squamous carcinoma xenografts. Results MTT assay showed that LCA significantly decreased the viability of H226 cells with an IC50 of 28.3 μmol/L at 48 h. Flow cytometry suggested that LCA treatment induced obvious cell cycle arrest at the G1 phase. LCA treatment also significantly decreased the expressions of cyclin D1, CDK2, and CDK4, and inhibited the phosphorylation of PI3K and Akt in H226 cells. In the tumor-bearing mice, LCA treatment for 24 days significantly reduced the tumor volume and weight. Conclusion LCA is capable of inhibiting theproliferation and inducing cell cycle arrest in lung squamous carcinoma cells possibility by regulating the PI3K/Akt singling pathway.

Key words: licochalcone A; cell proliferation; cell cycle; PI3K/Akt signaling pathway