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D.Y. Hur
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P2.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 234)
- Event: WCLC 2015
- Type: Poster
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P2.04-013 - TraiL Mediates Erlotinib-Induced Apoptosis in EGFR-Mutant Lung Cancer 3D Spheroids (ID 2872)
09:30 - 09:30 | Author(s): D.Y. Hur
- Abstract
Background:
Three-dimentional (3D) spheroid culture model were known to be a good model to study of the multicellular apoptotic resistance in most cancer cell lines. Contrary to the result with other cancer cell lines, we found that 3D spheroids of EGFR-mutant lung cancer cell lines showed more prominent apoptosis to tyrosine-kinase inhibitor (TKI), erlotinib than 2D monolayers in our previous experiments. BIM (the proapoptotic BH3-only BCL-2 family protein) expressions before and/or after treatment of TKI were more prominent in 3D than 2D in several EGFR-mutant lung cancer cell lines. But the other mechanisms of 3D sensitivity to TKI treatment are not studied yet.
Methods:
We used EGFR-mutant cell line, HCC4006 and A549 without EGFR mutation and generated 3D spheroids using poly-HEMA-coated 96-well plates. 2D monolayers and 3D spheroids were treatment with erlotinib. The degree of apoptosis were compared between 2D and 3D. Also the BIM and TNF-related apoptosis-inducing ligand (TraiL) expression were compared. After finding of relatively elevated TraiL expression in 3D, we silenced TraiL by siRNA and compared the degree of apoptosis between 2D and 3D.
Results:
We found that only HCC4006 not A549 showed apoptosis and elevated BIM expression after Erlotinib treatment. In line with our previous results, 3D spheroids showed more apoptosis and elevated BIM expression after Erlotinib treatment compared to 2D. Also we found more elevated TraiL expression in 3D. So we assumed that TraiL is one of the possible mechanisms of more apoptosis to Erlotinib in EGFR-mutant lung cancer 3D spheroids. After silencing the TraiL by siRNA, we found that there was no difference in the degree of apoptosis between 3D spheroids and 2D monolayer.
Conclusion:
Adding to increased BIM, we can suggest that elevated TraiL expression can be one of the possible mechanisms of the more prominent apoptosis in 3D spheroids of EGFR-mutant lung cancer cell lines. So potential therapies that upregulate BIM and/or TraiL expression can improved the efficacy of TKI treatment.
