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
3441 - The SWI/SNF driven reprograming for the AR cistrome is NSD2 dependent
Presenter: Katia Ruggero
Session: Poster Display session 1
Resources:
Abstract
1659 - IGF1R inhibition affects the survival of HT29 cancer cells by alterations of the TLR9- and autophagy signaling
Presenter: Györgyi Műzes
Session: Poster Display session 1
Resources:
Abstract
1379 - Characterization of atypical dMMR (deficient MisMatch Repair) tumors: a study from a large cohort of 4948 cases
Presenter: Marion Jaffrelot
Session: Poster Display session 1
Resources:
Abstract
1657 - Modulation of TLR9-dependent autophagy response via inhibition of c-Met signaling influences the survival of HT29 cancer cells
Presenter: Ferenc Sipos
Session: Poster Display session 1
Resources:
Abstract
3045 - Positive Feedback Activation of Notch Signal by Obesity Enhances Colorectal Tumorigenicity
Presenter: Dake Chu
Session: Poster Display session 1
Resources:
Abstract
2285 - The Pathological and Functional Roles of BRPF1 in Hepatocellular Carcinoma
Presenter: Lai Hung Carol Cheng
Session: Poster Display session 1
Resources:
Abstract
3210 - Protein tyrosine phosphatase non-receptor type 3 (PTPN3) could be a new therapeutic target for pancreatic cancer.
Presenter: Akio Yamasaki
Session: Poster Display session 1
Resources:
Abstract
3920 - A Novel bispecific BCMAxCD3 T cell engaging antibody that treat multiple myeloma (MM) with minimal cytokine serection
Presenter: Zhenyu Li
Session: Poster Display session 1
Resources:
Abstract
2691 - Quantitative spatial profiling of lymphocyte-activation gene 3 (LAG-3)/major histocompatibility complex class II (MHC II) interaction in gastric and urothelial tumors
Presenter: Cyrus Hedvat
Session: Poster Display session 1
Resources:
Abstract
2182 - Evaluating the prevalence of the expression of PD-L1 in NSCLC specimens with short-duration formalin fixation using IHC 22C3 pharmDx
Presenter: Keiichi Ota
Session: Poster Display session 1
Resources:
Abstract