EVALUATION OF THE EFFECTS OF WEE1 INHIBITOR ADAVOSERTIB ON GLIOBLASTOMA CELLS

Khac Cuong Bui1,2,3, Duc Trung Phan2,4, Thi Mai Ly Nguyen5,
1 Khoa Y học Thực nghiệm, Bệnh viện Trung ương Quân đội 108
2 Trung tâm Nghiên cứu Động vật Thực nghiệm, Học viện Quân y
3 Bộ môn Sinh lý bệnh, Học viện Quân y
4 Trường Đại học Dược Hà Nội
5 Bộ môn - Khoa Sinh hóa, Bệnh viện Quân y 103, Học viện Quân y

Main Article Content

Abstract

Objectives: To evaluate the inhibitory effect of Adavosertib (a WEE1 inhibitor) on the proliferation, colony formation, and migration of glioblastoma-derived U-87MG cell line. Methods: The study utilized WEE1 inhibitor - Adavosertib and glioblastoma cell line U-87MG. Cell proliferation assay, Crystal Violet staining, and cell migration were used to assess the inhibitory effects on cell viability, colony formation, and cell migration. Results: Adavosertib altered U-87MG cell morphology and viability in a dose-dependent manner. At 0.125µM, cell viability was approximately 75% compared to the controls; at 0.25µM and 0.5µM, viability declined sharply to about 40% and 30% compared to the controls, respectively, yielding an IC₅₀ of 0.2334µM. Crystal Violet staining demonstrated a marked, dose-dependent reduction in cell colony formation. In addition, Adavosertib significantly inhibited U-87MG cell migration in a dose-dependent fashion. Conclusion: Adavosertib had the ability to inhibit cell proliferation, colony formation, and reduce the migration ability of glioblastoma cells in vitro

Article Details

References

1. National Brain Tumor Society. About Glioblastoma. Natl Brain Tumor Soc.
2. Music D, Dahlrot RH, Hermansen SK, et al. Expression and prognostic value of the WEE1 kinase in gliomas. J Neurooncol. 2016; 127(2):381-389. DOI: 10.1007/s11060-015-2050-4.
3. Ghelli Luserna di Rorà A, Cerchione C, Martinelli G, Simonetti G. A WEE1 family business: Regulation of mitosis, cancer progression, and therapeutic target. J Hematol Oncol 2020; 13(1):126. DOI: 10.1186/s13045 -020-00959-2.
4. Cetin MH, Rieckmann T, Hoffer K, et al. G2 checkpoint targeting via Wee1 inhibition radiosensitizes EGFRvIII-positive glioblastoma cells. Radiat Oncol. 2023; 18(1):19. DOI: 10.1186/s13014-023-02210-x.
5. Roering P, Siddiqui A, Heuser VD, et al. Effects of Wee1 inhibitor adavosertib on patient-derived high-grade serous ovarian cancer cells are multiple and independent of homologous recombination status. Front Oncol. 2022; 12:954430. DOI: 10.3389/fonc.2022.954430.
6. Shuning Bi, Qiuren Wei, Zhijun Zhao, Liang Chen, Chaojie Wang, Songquang Xie. Wee1 Inhibitor AZD1775 Effectively inhibits the malignant phenotypes of esophageal squamous cell carcinoma in vitro and in vivo. ResearchGate. Published online August 2, 2019. DOI: 10.3389/fphar. 2019.00864.
7. Webster PJ, Littlejohns AT, Gaunt HJ, et al. Upregulated WEE1 protects endothelial cells of colorectal cancer liver metastases. Oncotarget. 2017; 8(26):42288-42299. DOI: 10.18632/ oncotarget.15039.
8. Kim HY, Cho Y, Kang H, et al. Targeting the WEE1 kinase as a molecular targeted therapy for gastric cancer. Oncotarget. 2016; 7(31):49902-49916. DOI: 10.18632/oncotarget.10231.