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Xingxiao Pill Suppressed the Progression of Non-Small Cell Lung Cancer by Targeting SREBP1/FASN-Induced Fatty Acid
Xiangnan Zhou1,2, Xiuhua Hu2,3, Zhiying Zhang2
1Department of Dermatology, China-Japan Friendship Hospital, National Center for Integrated Traditional Chinese and Western Medicine, Beijing, 100029, People's Republic of China.
Introduction:
Xingxiao Pill (XXP), a typical traditional Chinese medicine (TCM) prescription drug used to treat NSCLC in clinic. However, the mechanism underlying its regulatory effects remains unclear. This study aimed to evaluate the potential efficacy of XXP in treating NSCLC and to investigate how XXP regulates fatty acid biosynthesis in NSCLC.
Methods:
A lung carcinoma mouse model was created by transplanting Lewis lung carcinoma (LLC) cells into male C57BL/6 mice. Lung cancer cell models using LLC and A549 cells were also constructed. XXP's therapeutic efficacy on NSCLC was assessed via oral gavage. Bioinformatics analysis and transcriptome sequencing identified XXP's potential targets and mechanisms. These findings were verified by in vitro cell assays, Western blotting, immunofluorescence staining, and Oil Red O staining.
Results:
XXP inhibited lung tumor growth, suppressed cell proliferation and impeded cell migration. Additionally, it influenced the processes of apoptosis and cell cycle in both A549 and LLC cells. Bioinformatics analysis suggested that regulation of fatty acid biosynthesis and phosphoinositide-3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway were crucial mechanisms underlying the antitumor effects of XXP in lung cancer. XXP reduced the levels of the fatty acid biosynthesis products, such as total cholesterol (TC), triglycerides (TG), lipids, and free fatty acids in A549 cells, and downregulated the expression of sterol regulatory element binding protein 1 (SREBP1) and fatty acid synthase (FASN). Furthermore, XXP decreased the expression level of PI3K, AKT, mTOR, phospho-PI3K, and phospho-AKT.
Discussion:
XXP exerts its inhibitory effect on lung cancer tumor growth by controlling the biosynthesis of fatty acids and the PI3K/AKT/mTOR signaling pathway. The research suggests that targeting this metabolic pathway could be a viable strategy for cancer therapy and emphasizes the value of TCM in providing a rich source of innovative pharmaceuticals for cancer treatment.
Insights
Xingxiao Pill (XXP) effectively inhibits non-small cell lung cancer (NSCLC) growth by regulating fatty acid biosynthesis and the PI3K/AKT/mTOR pathway. This traditional Chinese medicine offers a promising metabolic strategy for lung cancer therapy.
Area of Science:
- Oncology
- Pharmacology
- Biochemistry
Background:
- Xingxiao Pill (XXP) is a traditional Chinese medicine used clinically for non-small cell lung cancer (NSCLC).
- The precise mechanisms by which XXP exerts its therapeutic effects on NSCLC remain largely unelucidated.
- Understanding XXP's molecular targets is crucial for optimizing its clinical application and developing novel cancer therapies.
Purpose of the Study:
- To evaluate the efficacy of Xingxiao Pill (XXP) in treating non-small cell lung cancer (NSCLC).
- To investigate the molecular mechanisms underlying XXP's regulation of fatty acid biosynthesis in NSCLC.
- To explore the potential of targeting metabolic pathways for NSCLC treatment.
Main Methods:
- Established a lung carcinoma mouse model using Lewis lung carcinoma (LLC) cells and constructed lung cancer cell models with LLC and A549 cells.
- Administered XXP via oral gavage to assess therapeutic efficacy in NSCLC.
- Employed bioinformatics analysis, transcriptome sequencing, in vitro cell assays, Western blotting, immunofluorescence, and Oil Red O staining to identify and verify XXP's targets and mechanisms.
Main Results:
- XXP significantly inhibited lung tumor growth, suppressed cell proliferation, and impeded cell migration in NSCLC models.
- XXP modulated apoptosis and cell cycle processes in A549 and LLC cells.
- Bioinformatics analysis revealed that XXP regulates fatty acid biosynthesis and the phosphoinositide-3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway, reducing key metabolites and downregulating crucial enzymes like sterol regulatory element binding protein 1 (SREBP1) and fatty acid synthase (FASN), as well as PI3K/AKT/mTOR pathway components.
Conclusions:
- Xingxiao Pill (XXP) inhibits lung cancer progression by modulating fatty acid biosynthesis and the PI3K/AKT/mTOR signaling pathway.
- Targeting these metabolic pathways presents a viable therapeutic strategy for NSCLC.
- This study highlights the therapeutic potential of traditional Chinese medicine in cancer treatment.
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