Effect of Guiqi Yiyuan Ointment Combined with Cisplatin on Mice with Lewis Lung Cancer Through Endoplasmic Reticulum Stress Pathway and Mitochondrial Apoptosis Pathway
10.13422/j.cnki.syfjx.20241022
- VernacularTitle:归芪益元膏联合顺铂通过内质网应激途径和线粒体凋亡途径对Lewis肺癌小鼠的影响
- Author:
Siqi KONG
1
;
Jintian LI
1
;
Juan LI
2
;
Jianqing LIANG
1
;
Yi ZHANG
1
;
Yue ZHANG
1
;
Chao YUAN
1
Author Information
1. The Clinical College of Traditional Chinese Medicine， Gansu University of Chinese Medicine， Lanzhou 730101， China
2. School of Basic Medicine， Gansu University of Chinese Medicine， Lanzhou 730101， China
- Publication Type:Journal Article
- Keywords:
Guiqi Yiyuan ointment;
lung cancer;
cisplatin;
mitochondrial apoptosis pathway;
endoplasmic reticulum stress pathway
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2024;30(20):54-61
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo explore the effects of Guiqi Yiyuan ointment combined with cisplatin on mice with Lewis lung cancer through the endoplasmic reticulum stress pathway and mitochondrial apoptosis pathway. MethodFifty SPF male C57BL/6 mice were randomly divided into the model group， cisplatin group （0.005 g·kg-1）， and low， medium， and high dose groups of Guiqi Yiyuan ointment combined with cisplatin （0.005+1.6 g·kg-1， 0.005+3.3 g·kg-1， and 0.005+6.6 g·kg-1）. Lewis cell suspension was inoculated under the axilla of mice in each group to construct the Lewis lung cancer xenograft mouse model. After continuous administration for 14 days， the mice were sacrificed. The body weight of the mice was measured， and the tumor weight was measured after the tumors were removed. The organ index and tumor inhibition rate were calculated. Hematoxylin-eosin （ HE） staining was used to observe the pathological changes in tumor tissue. Flow cytometry was used to detect the apoptosis rate of tumor cells and the ratio of reactive oxygen species （ROS）. Western blot was used to detect the expression of glucose-regulated protein 78 （GRP78）， phosphorylated activated protein kinase R-like endoplasmic reticulum kinase （p-PERK）， activated transcription factor 4 （ATF4）， and apoptosis protein C/EBP homologous protein （CHOP） in the endoplasmic reticulum stress pathway， as well as cysteine aspartate protease-9 （Caspase-9）， B-cell lymphoma-2（Bcl-2）， and Bcl-2 associated X protein（Bax） in the mitochondrial apoptosis pathway. ResultCompared with those in the model group， the mice in the groups of Guiqi Yiyuan Ointment combined with cisplatin had shinier fur and better mental response status. Tumor mass was reduced in all treatment groups （P<0.05）， and tumor inhibition rate was increased in all treatment groups （P<0.05）. The thymus and spleen indices of the combined group were increased （P<0.05）， and obvious pathological changes were observed in the tumor tissue of all treatment groups， with a gradual decrease in heteromorphism. Destruction of massive tumor tissue was observed in the high-dose combined group， and the apoptosis rate and ROS generation rate of tumor cells were increased in all treatment groups （P<0.05）. The protein expression level of Bcl-2 in the tumor tissue gradually decreased （P<0.05）， while the protein expression levels of GRP78， p-PERK， ATF4， CHOP， Bax， and Caspase-9 were significantly increased （P<0.05）. Compared with the cisplatin group， tumor mass was reduced in the combined group （P<0.05）， and tumor inhibition rates in the low and high-dose combined groups were increased （P<0.05）. The thymus index， spleen index， apoptosis rate of tumor cells， and ROS ratio in the combined group were significantly increased （P<0.05）， while the protein expression levels of GRP78， p-PERK， Bax， and Caspase-9 were increased in the low and high-dose combined groups （P<0.05）. The protein expression levels of ATF4 and CHOP were increased in the combined group （P<0.05）， while the expression level of Bcl-2 protein gradually decreased （P<0.05）. ConclusionGuiqi Yiyuan ointment combined with cisplatin can exert anti-tumor effects in mice with Lewis lung cancer， reduce tumor mass， increase tumor inhibition rate， and induce apoptosis of lung cancer cells. Its mechanism may be related to the regulation of the endoplasmic reticulum stress pathway and mitochondrial apoptosis pathway.
