Abstract
We propose a new in vitro model to assess the impact of 90Y-microspheres derived low-dose beta radiation on colorectal cancer cell line under various oxygenation conditions that mimic the tumor environment. Cancer cells (HCT116) proliferation was assessed using Alamar Blue (AB) assay after 48, 72, and 96 h. FLUKA code assessed changes in cancer cell populations relative to the absorbed dose. In normoxia, mitochondrial activity measured by Alamar Blue after 48–72 h was significantly correlated with the number of microspheres (48 h: r = 0.87 and 72 h: r = 0.89, p < 0.05) and absorbed dose (48 h: r = 0.87 and 72 h: r = 0.7, p < 0.05). In hypoxia, the coefficients were r = 0.43 for both the number of spheres and absorbed dose and r = 0.45, r = 0.47, respectively. Impediment of cancer cell proliferation depended on the absorbed dose. Doses below 70 Gy could reduce colorectal cancer cell proliferation in vitro. Hypoxia induced a higher resistance to radiation than that observed under normoxic conditions. Hypoxia and radiation induced senescence in cultured cells. The new in vitro model is useful for the assessment of 90Y radioembolization effects at the micro-scale.
Highlights
We propose a new in vitro model to assess the impact of 90Y-microspheres derived low-dose beta radiation on colorectal cancer cell line under various oxygenation conditions that mimic the tumor environment
A number of randomized controlled clinical trials have shown a positive effect of selective internal radiation therapy (SIRT) on response to treatment, in terms of time to progression and progression-free survival in metastatic colorectal cancer in the liver
In SIRT treatment, Yttrium-90 is used as a source of beta radiation, which is bound to resin or glass microspheres injected into the hepatic artery
Summary
We propose a new in vitro model to assess the impact of 90Y-microspheres derived low-dose beta radiation on colorectal cancer cell line under various oxygenation conditions that mimic the tumor environment. A number of randomized controlled clinical trials have shown a positive effect of selective internal radiation therapy (SIRT) on response to treatment, in terms of time to progression and progression-free survival in metastatic colorectal cancer (mCRC) in the liver. A key contributor to tumor resistance to radiation may be the oxygenation level at which the tumor grows This means that in lower oxygen conditions, many tumor cells are able to survive by developing mechanisms of adaptation to both hypoxia and radiation[14,15,16]. Toxicity relies on free radical formation, which depends on the availability of oxygen since these are mainly oxygen species These processes participate in the selection of hypoxia-tolerant and hypoxia-intolerant apoptosis-resistant cancer cells[17]. This feature may be transmitted between cancer cells by extracellular vesicles[17] and may lead to the clinical failure of radioembolization
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