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.

PubMed
Abstract

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.

Related Concept Videos

Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
7.8K
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
4.0K
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
9.2K