FoxO3a induces temozolomide resistance in glioblastoma cells via the regulation of β-catenin nuclear accumulation
Authors: Liang Li
Ke Xu
Zhenhao Zhang
Qianfeng Xia
Hua Pei
Huamin Wang
Journal: Oncology Reports (2017)
Discipline: CLINICAL MEDICINE
Keywords: Glioblastoma multiforme; TMZ resistance; FoxO3a; β-catenin; proliferation
Affiliations: Department of Immunology, School of Tropical and Laboratory Medicine, Hainan Medical University, Haikou, Hainan 571101, P.R. China., Medical Technology Institute of Xuzhou Medical University, Xuzhou, Jiangsu 221004, P.R. China., Key Laboratory of Tropical Biomedicine, and Faculty of Tropical Medicine and Laboratory Medicine, Hainan Medical University, Haikou, Hainan 571101, P.R. China.

Abstract:  Glioblastoma multiforme (GBM), the most common malignant brain tumor, is currently treated with temozolomide (TMZ), but GBM often exhibits resistance to TMZ. Although several mechanisms underlying GBM resistance to TMZ have been identified, these mechanisms are yet to fully explain how GBM gains resistance to TMZ. Our previous work has shown that FoxO3a, a member of the FoxO subfamily of transcription factors, promotes glioma cell proliferation and invasion. In this study, we sought to determine whether FoxO3a participates in TMZ resistance in GBM cells. Parental cell lines (also designated as sensitive cell lines) U87-MG and U251-MG, as well as the corresponding resistant cell lines U87-TR and U251-TR (generated by repeated TMZ treatments), were subjected to western blot analysis. Our results showed that the resistant cells (both U87-TRand U251-TR) exhibited higher levels of FoxO3a and β-catenin relative to their corresponding sensitive counterparts. Depletion of FoxO3a in the resistant cells enhanced the cytotoxic effect of TMZ. Further investigation showed that FoxO3a depletion did not affect the total protein level of β-catenin, but otherwise markedly reduced the nuclear β-catenin level. Taken together, these findings strongly support that FoxO3a renders GBM cells resistant to TMZ treatment, at least in part, through the regulation of β-catenin nuclear accumulation. 

Retracted: No

PubPeer comments:
 Figure 4. * Red boxes: In the left panels, the NC and FoxO3a-KD panels appear to show an overlap. Marked for the merged panels, but visible in the monoexposures as well. ![file]  We thank the National Natural Science Foundation of China (grant no. 81660502) and the Start-up Foundation for Young Scientists of Hainan Medical University (2015012) for funding this study. , 
 Corrigendum, November 2020: https: www.spandidos-publications.com 10.3892 or.2020.7842  Following the publication of the above article, an interested reader drew to the authorsu2019 attention that an error was made in the assembly of the data panels shown in Fig. 4A. The u2018NCu2019 and u2018FoxO3a-KDu2019 panels (specifically, the upper left margins of the three u2018NCu2019 data panels and the lower right margins of the three u2018FoxO3a-KDu2019 panels) contained overlapping data. The authors were able to consult their original data, and realized that errors had occurred inadvertently during the figure compilation process. The revised version of Fig. 4A, featuring the corrected data panels for the u2018NCu2019 experiments, is shown opposite. The authors have confirmed that the errors associated with this figure did not have any significant impact on either the results or the conclusions reported in this study, and are grateful to the Editor of Oncology Reports for allowing them the opportunity to publish this Corrigendum. Furthermore, they apologize to the readership of the Journal for any inconvenience caused. I thank the authors and journal for correcting this error. ,