Abstract 4855
Background
IDH1 R132H mutant (IDH1R132H) glioma patients have better prognosis compared with IDH1 wild-type (IDH1wt) patients. However, the molecular mechanism is largely unknown. In this study, we investigated the biological behaviors of IDH1R132H and IDH1wt glioma cells, intends to explore whether the IDH1R132H protein could affect radiosensitivity. Additionally, we studied potential cross-talk between IDH1 and Wnt/β-catenin signaling in regulating radioresistance.
Methods
We established stable transfected U87MG and SY5Y cell lines with IDH1R132H or IDH1wt gene. The proliferation, migration and invasion ability were determined respectively by CCK-8, wound healing assay and Transwell assay. The radiosensitivity was detected by colony formation assay after 0, 2, 4, 6, 8, 10Gy radiation. Using Western blot, we assayed changes in β-catenin protein of glioma cells before and after 10 Gy radiation.
Results
The glioma cells were divided into three groups: blank control group, IDH1R132H group and IDH1wt group after stable transfection. CCK-8 assay showed that proliferation was significantly decreased in IDH1R132H group. Wound healing assay and Transwell migration assay both showed that migration capacity of IDH1R132H group was reduced than the other two groups. Transwell invasion assay also showed that IDH1R132H group has the lowest invasion rate. After 10Gy radiation, the proliferation, migration and invasion ability of IDH1R132H group was further lower than the other two groups. Similarly, colony formation assay showed formation rate of IDH1R132H group was reduced than the other groups. Western blot revealed that β-catenin protein was declined in IDH1R132H group. Furthermore, after 10Gy radiation, β-catenin protein increased in all three groups, but it was more obvious in IDH1wt group.
Conclusions
These data suggest that IDH1R132H mutation leads to a less aggressive biological behavior and increase the radiosensitivity. The molecular mechanism may be that IDH1 can activate the Wnt/β-catenin signaling pathway. Radiotherapy in combination with inhibitor of Wnt/β-catenin signaling may be an attractive approach for IDH1wt glioma patients.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The Second Hospital of Hebei Medical University.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
3690 - PD-L1 expression in resected undifferentiated pleomorphic sarcoma and its clinical implications
Presenter: Kyoungmin Lee
Session: Poster Display session 1
Resources:
Abstract
2013 - PD-L1 expression as a potential therapeutic target and prognostic biomarker in well-differentiated and dedifferentiated liposarcoma.
Presenter: Heejung Chae
Session: Poster Display session 1
Resources:
Abstract
5021 - Soft tissue sarcomas express a distinct mRNA immune profile
Presenter: Viktor Grünwald
Session: Poster Display session 1
Resources:
Abstract
3029 - The molecular landscape of fusion genes in endometrial stromal sarcomas include three nosological entities with different natural history
Presenter: Mehdi Brahmi
Session: Poster Display session 1
Resources:
Abstract
3914 - Clinical validation of a novel assay for the detection of diagnostic alterations in sarcomas
Presenter: Lauren Mc Connell
Session: Poster Display session 1
Resources:
Abstract
1912 - A prospective correlative trial of personalized patient-derived xenograft (PDX) as avatars for drug therapy in patients with metastatic or recurrent soft tissue sarcomas (STS).
Presenter: Kanan Alshammari
Session: Poster Display session 1
Resources:
Abstract
5097 - Fusion of immortalized myoblasts induces genomic instability that drives tumor development and progression.
Presenter: Candice Merle
Session: Poster Display session 1
Resources:
Abstract
1383 - let-7a suppress Ewing sarcoma CSCs' malignant phenotype through forms a positive feedback regulation loop with lin28 via STAT3
Presenter: Xu Jiang
Session: Poster Display session 1
Resources:
Abstract
3386 - Myoepithelial Tumors of Soft Tissues and Extraskeletal Myxoid Chondrosarcomas feature a distinct transcriptional pattern
Presenter: Dominga Racanelli
Session: Poster Display session 1
Resources:
Abstract
1844 - In Vivo Efficacy and Enhanced Tumor Accumulation of Liposomal Vinorelbine (TLC178) in Human Sarcoma Xenograft Mice Model
Presenter: Wan-ni Yu
Session: Poster Display session 1
Resources:
Abstract