Hydrogen gas inhibits lung cancer progression through targeting SMC3

Dongchang Wang1, Lifei Wang1, Yu Zhang1

  • 1Department of Respiration, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.

Insights

Hydrogen gas (H2) effectively inhibits lung cancer progression by down-regulating structural maintenance of chromosomes 3 (SMC3), a key regulator of chromosome condensation. This offers a promising new therapeutic strategy for lung cancer treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Gas Therapy

Background:

  • Lung cancer remains a leading cause of cancer-related deaths globally.
  • High metastatic potential and drug resistance contribute to poor patient prognoses.
  • Novel therapeutic strategies are urgently needed to improve lung cancer treatment outcomes.

Purpose of the Study:

  • To investigate the therapeutic potential of hydrogen gas (H2) in lung cancer.
  • To elucidate the molecular mechanisms underlying H2's effects on lung cancer cells.
  • To evaluate the role of structural maintenance of chromosomes 3 (SMC3) in H2-mediated anti-cancer effects.

Main Methods:

  • Cell viability, apoptosis, migration, and invasion assays (CCK-8, flow cytometry, wound healing, Transwell).
  • RNA sequencing (RNA-seq), quantitative PCR (qPCR), and Western blotting to identify differentially expressed genes.
  • In vitro and in vivo experiments using lung cancer cell lines (A549, H1975) and a mouse xenograft model.

Main Results:

  • H2 significantly inhibited lung cancer cell viability, migration, and invasion while promoting apoptosis and G2/M cell cycle arrest.
  • H2 downregulated key genes including NIBPL, SMC3, SMC5, SMC6, Cyclin D1, CDK4, and CDK6.
  • H2 treatment disrupted SMC3 subcellular localization, decreased its stability, and increased its ubiquitination, effects reversed by SMC3 overexpression.

Conclusions:

  • H2 inhibits lung cancer progression by down-regulating SMC3, a regulator of chromosome condensation.
  • SMC3 plays a critical role in H2-mediated inhibition of proliferation, migration, and invasion, and promotion of apoptosis.
  • H2 represents a potential novel therapeutic agent for lung cancer treatment.

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