Activating PTEN by COX-2 inhibitors antagonizes radiation-induced AKT activation contributing to radiosensitization

Biochemical and Biophysical Research Communications
Zhen Meng, Ye-Hua Gan

Abstract

Radiotherapy is still one of the most effective nonsurgical treatments for many tumors. However, radioresistance remains a major impediment to radiotherapy. Although COX-2 inhibitors can induce radiosensitization, the underlying mechanism is not fully understood. In this study, we showed that COX-2 selective inhibitor celecoxib enhanced the radiation-induced inhibition of cell proliferation and apoptosis in HeLa and SACC-83 cells. Treatment with celecoxib alone dephosphorylated phosphatase and tensin homolog deleted on chromosome ten (PTEN), promoted PTEN membrane translocation or activation, and correspondingly dephosphorylated or inactivated protein kinase B (AKT). By contrast, treatment with radiation alone increased PTEN phosphorylation, inhibited PTEN membrane translocation and correspondingly activated AKT in the two cell lines. However, treatment with celecoxib or another COX-2 selective inhibitor (valdecoxib) completely blocked radiation-induced increase of PTEN phosphorylation, rescued radiation-induced decrease in PTEN membrane translocation, and correspondingly inactivated AKT. Moreover, celecoxib could also upregulate PTEN protein expression by downregulating Sp1 expression, thereby leading to the activation of PTEN...Continue Reading

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Citations

Jun 27, 2017·Anti-cancer Drugs·Xia ChenJufang Huang
Sep 22, 2019·Cells·Wanyeon KimBuHyun Youn
Mar 9, 2019·Journal of Bioenergetics and Biomembranes·Seyed Jalal HosseinimehrHossein Asgarian-Omran
Jul 5, 2018·Cancer Metastasis Reviews·Wanyeon KimBuHyun Youn
Dec 15, 2020·Critical Reviews in Oncology/hematology·Chiman MohammadiRezvan Najafi
Dec 6, 2016·European Journal of Pharmacology·Ping XuDan-Dan Lu

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