Caspase-8 knockdown suppresses apoptosis, while induces autophagy and chemo-sensitivity in non-small cell lung cancer

Hui Zuo1,2, Cheng Chen1, Ling Ma1,2

  • 1Department of Pharmacology, The First People's Hospital of Yunnan Province Kunming 650032, Yunnan Province, China.

Abstract

Insights

Reducing caspase-8 levels in non-small cell lung cancer (NSCLC) cells enhances cell growth and autophagy but decreases chemo-sensitivity and apoptosis. Caspase-8 may be a target to improve NSCLC treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Drug resistance is a primary challenge in non-small cell lung cancer (NSCLC) treatment, leading to relapse and therapeutic failure.
  • Understanding molecular mechanisms underlying chemo-resistance is crucial for developing effective therapies.

Purpose of the Study:

  • To investigate the role of caspase-8 in chemo-sensitivity and its underlying mechanisms in NSCLC cells.
  • To explore the relationship between caspase-8 expression levels and response to chemotherapy drugs.

Main Methods:

  • Utilized A549 NSCLC cell line with manipulated caspase-8 levels via lentiviral shRNA and overexpression plasmids.
  • Assessed cell viability (CCK-8 assay), apoptosis (Annexin V-FITC/PI staining), and autophagy (acridine orange staining).
  • Quantified mRNA and protein expression using qRT-PCR and western blotting.

Main Results:

  • Knockdown of caspase-8 significantly reduced apoptosis and the Bcl-2/Bax ratio in A549 cells.
  • Caspase-8 knockdown promoted autophagy and decreased sensitivity to doxorubicin, carboplatin, cisplatin, and etoposide.
  • Overexpression studies were also conducted to further elucidate caspase-8's role.

Conclusions:

  • Caspase-8 knockdown promotes NSCLC cell growth and autophagy while diminishing chemo-sensitivity and apoptotic cell death.
  • These findings suggest that caspase-8 could be a potential therapeutic target to enhance chemo-sensitivity in NSCLC patients.
  • Modulating caspase-8 levels may offer a novel strategy to overcome drug resistance in lung cancer.

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