Effect of Lifei Xiaoji Pill (理肺消积丸) on the Warburg Effect and USP47/BACH1 Pathway in Tumor Tissues of Lung Cancer Model Mice
10.13288/j.11-2166/r.2025.11.012
- VernacularTitle:理肺消积丸对肺癌模型小鼠肿瘤组织Warburg效应及USP47/BACH1通路的影响
- Author:
Suxiao LIU
1
;
Ruili ZHAO
2
;
Yu GU
2
;
Jinbeng DING
2
;
Yuebing CHEN
2
;
Suxiang FENG
3
;
Suyun LI
3
;
Ya LI
1
Author Information
1. Laboratory Center,The First Affiliated Hospital of Henan University of Chinese Medicine,Zhengzhou,450000
2. The First Clinical Medical College of Henan University of Chinese Medicine
3. Co-construction Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases by Henan Province and Education Ministry of P.R. China/Henan Provincial Key Laboratory of Chinese Medicine for Respiratory Disease Prevention and Treatment
- Publication Type:Journal Article
- Keywords:
lung cancer;
Warburg effect;
USP47;
BACH1;
energy metabolism;
Lifei Xiaoji Pill (理肺消积丸)
- From:
Journal of Traditional Chinese Medicine
2025;66(11):1157-1164
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo explore the possible mechanism of action of Lifei Xiaoji Pill (理肺消积丸, LXP) in the treatment of non small cell lung cancer based on the Warburg effect and the USP47/BACH1 pathway. MethodsFifty C57BL/6 mice were randomly divided into five groups, model group, LXP group, inhibitor group, LXP + inhibitor group, and cisplatin group, with 10 mice in each group. A lung cancer mouse model was established by subcutaneously injecting Lewis cells. On the next day, the model group mice were given 0.2 ml of saline by gavage daily, the LXP group given 240 mg/(kg·d) of LXP solution once a day by gavage, the inhibitor group intraperitoneally injected with P22077 at a dose of 10 mg/(kg·d) every day, the LXP + inhibitor group given both LXP by gavage and P22077 by intraperitoneal injection once a day, and the cisplatin group received 0.5 mg/(kg·d) cisplatin intraperitoneally every other day. All treatments lasted for 14 days. On the day after the last dose, tumor weight and volume were measured, tumor histopathology was examined by HE staining, apoptosis in tumor tissues was detected by TUNEL staining, and proliferation cell nuclear antigen (PCNA) protein levels were detected by immunohistochemistry. Warburg effect indicators, including glucose concentration, lactate content, and adenosine triphosphate (ATP) production in tumor tissues, were measured. Western Blot and qRT-PCR were used to detect the protein and mRNA expression levels of USP47, BACH1, hexokinase 2 (HK2), and glyceraldehyde 3-phosphate dehydrogenase (GAPDH). ResultsCompared with the model group, all drug intervention groups showed reduced tumor weight and volume, improved tumor pathology, decreased PCNA positive rate, increased apoptosis rate, and reduced expression levels of USP47, BACH1, and HK2 proteins and mRNA (P<0.05 or P<0.01). Except for lactate content in the cisplatin group, the glucose concentration in tumor tissues of other drug intervention groups increased, while lactate content and ATP production decreased (P<0.05 or P<0.01). Compared with the LXP group, the LXP + inhibitor group showed more significant improvements in these indicators (P<0.05 or P<0.01). Compared with the cisplatin group, the LXP + inhibitor group had lower mRNA expression of HK2 and GAPDH, and lower protein levels of USP47 and HK2 (P<0.05 or P<0.01). Compared with the inhibitor group, the cisplatin group had higher HK2 protein levels, while the LXP + inhibitor group showed lower mRNA expression of BACH1, HK2, and GAPDH (P<0.05 or P<0.01). ConclusionLXP significantly inhibits tumor growth in lung cancer mice, and its mechanism of action may be related to inhibiting the Warburg effect via the USP47/BACH1 pathway.