Kangai Injection Reverses Cisplatin Resistance through PI3K/Akt/mTOR Signaling Pathway Mediated Cell Cycle Arrest and Autophagic Death in A549/DDP Cells
- VernacularTitle:康艾注射液通过抑制PI3K/Akt/mTOR信号通路诱导细胞周期阻滞及自噬性死亡改善A549/DDP细胞顺铂耐药性的研究
- Author:
Jialu LYU
1
;
Huan ZHOU
;
Wenjun LIU
;
Jianguang WANG
;
Chung WANG
Author Information
- Publication Type:Journal Article
- Keywords: NSCLC; Cisplatin resistance; Kangai injection(KAI); Cycle arrest; Autophagy
- From: World Science and Technology-Modernization of Traditional Chinese Medicine 2024;26(12):3127-3135
- CountryChina
- Language:Chinese
- Abstract: Objective Targeting the cell cycle and autophagy,Kangai injection(KAI)was investigated through PI3K/Akt/mTOR Signaling pathways improve the molecular mechanism of cisplatin resistance in human lung adenocarcinoma A549/DDP cells.Methods A549/DDP cells were randomly divided into control group,cisplatin group(20 μmol·L-1 cisplatin),low concentration KAI combined with cisplatin(15 mg·mL-1 KAI+20 μmol·L-1 cisplatin),medium concentration KAI combined with cisplatin(25 mg·mL-1 KAI+20 μmol·L-1 cisplatin)and high concentration KAI combined with cisplatin(50 mg·mL-1 KAI+20 μmol·L-1 cisplatin).The survival rate of cells was detected by CCK-8 method,the cell cycle distribution was detected by flow cytometry,the expression of p53 protein was detected by immunocytochemistry,and the expression levels of protein p53、autophagy-related protein LC3 and key molecules of autophagy pathway(mTOR,p-mTOR,Akt and p-Akt)were detected by Western blotting.Besides,the inhibitor of PI3K/Akt signaling pathway was used to further verify the molecular mechanism of KAI in reversing cisplatin in A549/DDP cells.Results Compared with the control group,cisplatin group and different concentrations of KAI combined with cisplatin groups effectively inhibited cell viability(P<0.05);compared with the cisplatin group,increased the cell proportion in S+G2/M phase(P<0.05),the mean integral absorbance of p53 protein(P<0.05),and the expression level of autophagy-related protein LC3Ⅱ(P<0.05),but decreased the expression levels of p-mTOR and p-Akt(both P<0.01).Moreover,LY294002,the inhibitor of PI3K/Akt signaling pathway,could effectively inhibit the up-regulation of LC3Ⅱ expression and cell death induced by KAI combined with cisplatin(both P<0.05).Conclusion KAI combined with cisplatin can induce cell cycle arrest and autophagic death by inhibiting PI3K/Akt/mTOR signaling pathway,and improve cisplatin resistance in NSCLC.
