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F. Luo
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Poster Session (ID 8)
- Event: ACLC 2018
- Type: Poster Session
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 11/07/2018, 00:00 - 00:00, Poster Hall
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P100 - Stem Cell Factor Leads to Lung Cancer Escapes from Anti-Angiogenic Therapy by Increasing the ALDH1+ Lung Cancer Cell Number (ID 146)
00:00 - 00:00 | Author(s): F. Luo
- Abstract
Background:
Although the anti-angiogenic therapy becomes an important treatment for non-small-cell lung cancer, cancer cells can escape from this therapy through several different ways so as to keep growth. Our previous results showed that anti-angiogenic drugs increased the number of ALDH1+ lung cancer cells in mouse models. This study is to explore the significance and mechanism of this phenomenon.
Method:
The xenograft tumor murine models and molecular experiments in vitro were used in this study.
Results:
In our experiments with murine lung cancer xenografts, we found that the anti-angiogenic agent endostatin increased the number of ALDH1+ lung caner cells. In vitro results showed that SOX and OCT4 were highly expressed in ALDH1+ lung cancer cells. These cells had stronger ability in surviving in hypoxic environment, metastasis and invasion than ALDH1- lung cancer cells. We also found that the expressions of HIF-1a and stem cell factor (SCF) in the xenografts were increased after anti-angiogenic therapy. HIF-1? could up-regulate the expression of SCF in lung cancer cells. The over-expression of SCF can increase the proportion of ALDH1+ cells in lung cancer. The mechanism was related to the HIF-1?/SCF/c-Kit/PI3K/AKT pathway. Finally, when we combined anti-angiogenic therapy with decreasing SCF expression, it is found that the survival time of mice in the combination group was significantly longer than that in the single anti-angiogenic group.
Conclusion:
Anti-angiogenic therapy aggravated hypoxia which could induce the up-regulated expression of SCF in lung cancer. SCF promoted lung cancer to escape from anti-angiogenic therapy by increasing the number of ALDH1+ lung cancer cells.