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[A dual PI3K/mTOR inhibitor, PI-103, cooperates with TRAIL in laryngeal squamous carcinoma cells in vitro]

C L Gao1, K N Li, L Zhou

  • 1Department of Otorhinolaryngology, Eye Ear Nose and Throat Hospital, Fudan University, Shanghai 200031, China.

Zhonghua Yi Xue Za Zhi
|July 29, 2016
PubMed
Abstract

Insights

Combining PI-103, a dual phosphoinositide-3-kinase (PI3K)/mammalian target of rapamycin (mTOR) inhibitor, with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) enhances anti-tumor effects in laryngeal cancer cells. This combination therapy shows promise for treating laryngeal cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Laryngeal squamous carcinoma is a significant health concern.
  • Targeting the PI3K/AKT/mTOR pathway is a key strategy in cancer therapy.
  • Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has shown potential as an anti-cancer agent.

Purpose of the Study:

  • To investigate the synergistic anti-tumor effects of PI-103, a dual PI3K/mTOR inhibitor, combined with TRAIL on laryngeal cancer Hep-2 cells.
  • To evaluate the impact of this combination on cell cycle, apoptosis, migration, and invasion.
  • To examine the modulation of key proteins within the PI3K/AKT/mTOR signaling pathway.

Main Methods:

  • Hep-2 cells were treated with PI-103, TRAIL, or their combination.
  • Cell cycle progression and apoptosis were analyzed using flow cytometry.
  • Cell migration and invasion were assessed via Transwell assays.
  • Protein expression related to apoptosis and the PI3K/AKT/mTOR pathway was determined by Western blotting.

Main Results:

  • The combination of PI-103 and TRAIL induced S-phase cell cycle arrest and significantly enhanced apoptosis (66.78%).
  • Combined treatment markedly reduced Hep-2 cell migration and invasion compared to PI-103 alone.
  • PI-103 inhibited the PI3K/AKT/mTOR pathway by decreasing p-AKT and p-4E-BP1 expression, while increasing Caspase 9, 8, and 3 expression.

Conclusions:

  • The combination of PI-103 and TRAIL demonstrates enhanced anti-tumor activity against laryngeal cancer cells in vitro.
  • This combined therapeutic approach presents a promising strategy for the clinical management of laryngeal cancer.

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