Can Cancer Cell Line In Vitro Radioembolization Model Help to Understand How Beta Radiation Affects Liver Tumor and...

Area of Science:

• Oncology
• Radiation Oncology
• Molecular Biology

Background:

• Radioembolization using 90Y-labeled microspheres is a standard treatment for liver tumors.
• The molecular mechanisms of tumor response and resistance, especially in hypoxic conditions, are not fully understood.

Purpose of the Study:

• To investigate the effects of beta radiation from 90Y-microspheres on cancer cells under normoxic and hypoxic conditions.
• To elucidate the molecular mechanisms of radioembolization response and resistance in different liver cell types.

Main Methods:

• Developed an in vitro model using 90Y-microsphere irradiation on human colon cancer (HCT 116), hepatocellular carcinoma (HepG2), and non-malignant liver (THLE2) cells.
• Assessed cellular viability, proliferation, apoptosis-related gene expression, and secretion of angiogenic/inflammatory mediators.
• Estimated absorbed doses using FLUKA-based Monte Carlo simulations.

Main Results:

• 90Y-microspheres showed cell type- and oxygen-dependent cytotoxic and cytostatic effects.
• Hypoxia conferred radioresistance in HCT 116 cells (upregulating Bcl-2) but attenuated cytostatic effects in HepG2 cells.
• Hypoxia promoted a pro-angiogenic phenotype, increasing VEGF secretion in radiosensitive cells and altering signaling in resistant cells.

Conclusions:

• Hypoxia diminishes cellular sensitivity to 90Y beta radiation and promotes a tumor-promoting microenvironment.
• The in vitro model provides mechanistic insights into radioembolization, aiding personalized therapeutic strategies.