4855 - IDH1R132H mutation induces a less aggressive phenotype of glioma cells and affects the radiosensitivity by interacting with Wnt/β-catenin signaling

Background

IDH1 R132H mutant (IDH1^R132H) glioma patients have better prognosis compared with IDH1 wild-type (IDH1_wt) patients. However, the molecular mechanism is largely unknown. In this study, we investigated the biological behaviors of IDH1^R132H and IDH1_wt glioma cells, intends to explore whether the IDH1^R132H 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 IDH1^R132H or IDH1_wt 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, IDH1^R132H group and IDH1_wt group after stable transfection. CCK-8 assay showed that proliferation was significantly decreased in IDH1^R132H group. Wound healing assay and Transwell migration assay both showed that migration capacity of IDH1^R132H group was reduced than the other two groups. Transwell invasion assay also showed that IDH1^R132H group has the lowest invasion rate. After 10Gy radiation, the proliferation, migration and invasion ability of IDH1^R132H group was further lower than the other two groups. Similarly, colony formation assay showed formation rate of IDH1^R132H group was reduced than the other groups. Western blot revealed that β-catenin protein was declined in IDH1^R132H group. Furthermore, after 10Gy radiation, β-catenin protein increased in all three groups, but it was more obvious in IDH1_wt group.

Conclusions

These data suggest that IDH1^R132H 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 IDH1_wt 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.