Buzhong Yiqitang Induces Ferroptosis by Regulating PCBP1 to Attenuate Cisplatin Resistance in Non-small Cell Lung Cancer
10.13422/j.cnki.syfjx.20242328
- VernacularTitle:补中益气汤通过调控PCBP1诱导铁死亡改善非小细胞肺癌顺铂耐药的分子机制
- Author:
Yuetong LIU
1
;
He LI
1
;
Qirui MU
1
;
Jingyi HUANG
1
;
Haoran CAI
1
;
Chunying LIU
1
;
Yuan GAO
1
Author Information
1. College of Integrated Chinese and Western Medicine， Liaoning University of Traditional Chinese Medicine， Shenyang 110847， China
- Publication Type:Journal Article
- Keywords:
Buzhong Yiqitang;
non-small cell lung cancer （NSCLC）;
poly（rC）-binding protein 1 （PCBP1）;
ferroptosis;
cisplatin resistance
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2025;31(10):90-97
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo explore the molecular mechanism of Buzhong Yiqitang in attenuating cisplatin resistance in non-small cell lung cancer （NSCLC） by inducing ferroptosis via poly（rC）-binding protein 1 （PCBP1）. MethodsThe serum containing Buzhong Yiqitang was prepared and cisplatin-resistant human non-small cell lung cancer （NSCLC） cells （A549/DDP） were cultured and randomly grouped as follows： Blank （10% blank serum）， model （10% blank serum+20 mg·L-1 cisplatin）， Buzhong Yiqitang （10% serum containing Buzhong Yiqitang+20 mg·L-1 cisplatin）， Fe-1 （10% blank serum+20 mg·L-1 cisplatin+5 μmol·L-1 Fe-1）， and Buzhong Yiqitang+Fe-1 （10% serum containing Buzhong Yiqitang+20 mg·L-1 cisplatin+5 μmol·L-1 Fe-1）. Firstly， PCR Array was used to screen ferroptosis-related genes regulated by Buzhong Yiqitang， and PCBP1 was identified as the target for studying the attenuation of cisplatin resistance by Buzhong Yiqitang. Subsequently， the median inhibitory concentration （IC50） of cisplatin in each group was determined by the cell counting kit-8 （CCK-8） method and the resistance index （RI） was calculated. The ultrastructure of A549/DDP cells in each group was observed by transmission electron microscopy. The protein levels of PCBP1 and glutathione peroxidase 4 （GPX4） were determined by Western blot. The lipid reactive oxygen species （ROS） content in each group was determined by the C11-BODIRY 581/591 fluorescence probe. The ferrous ion assay kit was used to measure the ferrous ion content in each group. The malondialdehyde （MDA） assay kit was used to determine the MDA content in each group. ResultsCompared with model group， the IC50 of cisplatin and the RI of A549/DDP cells decreased in the Buzhong Yiqitang group （P<0.05） but increased in the Fe-1 group （P<0.05）. The IC50 of cisplatin and the RI of A549/DDP cells in the Buzhong Yiqitang+Fe-1 group were lower than those in the Fe-1 group （P<0.05）. Compared with the model group， the Buzhong Yiqitang group showed obvious mitochondrial ferroptosis， while the mitochondrial damage became less obvious after Fe-1 treatment. Compared with that in the Fe-1 group， the mitochondrial ferroptosis was aggravated after the intervention with Buzhong Yiqitang. Compared with blank group， the model group showed down-regulated expression levels of PCBP1 and GPX4 （P<0.05） and increased content of lipid ROS， ferrous ions， and MDA （P<0.05） in A549/DDP cells. Compared with model group， the Buzhong Yiqitang group showed down-regulated expression levels of PCBP1 and GPX4 （P<0.05） and increased content of lipid ROS， ferrous ions， and MDA （P<0.05）， while the Fe-1 group showed up-regulated expression levels of PCBP1 and GPX4 （P<0.05） and reduced content of lipid ROS， ferrous ions， and MDA （P<0.05）. Compared with the Fe-1 group， the Buzhong Yiqitang+Fe-1 group showed down-regulated expression levels of PCBP1 and GPX4 and increased content of lipid ROS， ferrous ions， and MDA （P<0.05）. ConclusionBuzhong Yiqitang attenuated cisplatin resistance in NSCLC by regulating PCBP1 to induce ferroptosis.
