Mechanisms of Shenmai Injection in Improving Cisplatin Resistance in Non-small Cell Lung Cancer
10.13422/j.cnki.syfjx.20251027
- VernacularTitle:参麦注射液改善非小细胞肺癌顺铂耐药作用机制
- Author:
Hanyu DONG
1
;
Chun WANG
2
;
Chunying LIU
2
;
Wenjun LIU
1
Author Information
1. Key Laboratory of Ministry of Education for Traditional Chinese Medicine（TCM） Viscera-State Theory and Applications， Liaoning University of TCM，Shenyang 110847，China
2. School of Basin Medical Sciences，Liaoning University of TCM，Shenyang 110847，China
- Publication Type:Journal Article
- Keywords:
non-small cell lung cancer;
cisplatin resistance;
Shenmai injection;
network pharmacology;
non-target metabolomics;
lipophagy;
ferroptosis
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2026;32(6):131-142
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo investigate whether Shenmai injection （SMI） improves cisplatin resistance in non-small cell lung cancer （NSCLC） by modulating lipid metabolism and inducing ferroptosis. MethodsHuman lung adenocarcinoma cisplatin-resistant A549/DDP cells were divided into the following groups： Blank group， cisplatin group （23.3 μmol·L-1 cisplatin）， SMI group （20 g·L-1 SMI）， cisplatin combined with SMI group （23.3 μmol·L-1 cisplatin + 20 g·L-1 SMI）， cisplatin combined with ferroptosis inhibitor/inducer Ferrostatin-1/Erastin group （23.3 μmol·L-1 cisplatin + 10 μmol·L-1 Ferrostatin-1/5 μmol·L-1 Erastin）， and cisplatin combined with SMI and Ferrostatin-1/Erastin group （23.3 μmol·L-1 cisplatin + 20 g·L-1 SMI + 10 μmol·L-1 Ferrostatin-1/5 μmol·L-1 Erastin）. Network pharmacology， transcriptomics and metabolomics， Cell Counting Kit-8 （CCK-8） assay， transmission electron microscopy （TEM）， colorimetric assays， and Western blot analysis were employed to evaluate the effects of these treatments on A549/DDP cell viability， lipid droplet formation， lipid metabolite levels， mitochondrial function， lipid peroxidation， glutathione （GSH） content， total and ferrous iron content， and effects on ferroptiosis and autophagy related protein expression levels. ResultsSMI improved cisplatin resistance in NSCLC mainly by targeting lipid metabolism-related pathways in A549/DDP cells， affecting tumor cell lipid metabolism via autophagy， ferroptosis， and glycerophospholipid metabolism pathways. Compared with the cisplatin group， the cisplatin combined with SMI group showed significantly decreased cell viability （P<0.01）， increased lipid droplet accumulation （P<0.01）， and reduced mitochondrial maximal respiration， basal respiration， mitochondrial membrane potential， GSH content， total iron， and ferrous iron （all P<0.01）. Mitochondrial reactive oxygen species （ROS） was significantly elevated（P<0.01）， and lipid peroxidation levels were significantly increased. Protein expression analysis showed significant downregulation of solute carrier family 7 member 11 （SLC7A11） and p62 （P<0.05，P<0.01） and upregulation of ferritin heavy chain （FTH） and microtubule-associated protein 1 light chain 3Ⅱ （LC3Ⅱ） （P<0.05，P<0.01）. Compared with the cisplatin combined with SMI group， addition of Ferrostatin-1 significantly increased cell viability （P<0.05）， decreased mitochondrial ROS levels （P<0.05）， alleviated mitochondrial shrinkage， and reduced lipid peroxidation. Conversely， addition of Erastin further decreased cell viability （P<0.01）. ConclusionSMI improves cisplatin resistance in NSCLC by inducing oxidative stress， which may trigger ferroptosis through upregulation of lipophagy.
