Drug Design, Development and Therapy (Apr 2021)
MYC/NBS1-Mediated DNA Damage Response is Involved in the Inhibitory Effect of Hydroxysafflor Yellow A on Glioma Cells
Abstract
Dongfang Tang,1 Tao Huang,2 Qilong Tian,2 Julei Wang2 1Department of Neurosurgery, Henan Provincial People’s Hospital, Central China Fuwai Hospital, Central China Fuwai Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China; 2Department of Neurosurgery, The Second Affiliated Hospital of Air Force Military Medical University, Xi’an City, People’s Republic of ChinaCorrespondence: Julei WangDepartment of Neurosurgery, The Second Affiliated Hospital of Air Force Military Medical University, No. 569 Xinsi Road, Baqiao District, Xi’an City, Shaanxi Province, 710038, People’s Republic of ChinaTel +86-29-84777777Email [email protected]: The role of Hydroxysafflor Yellow A (HSYA) in glioma is less studied, this research determined the effect of HSYA on glioma cells.Methods: The expressions of MYC and NBS1 in glioma tissues were detected by bioinformatics analysis and verified by RT-qPCR. The target relationship between MYC and NBS1 was predicted by bioinformatics. After treating the cells with HSYA, silenced MYC, or overexpressed NBS1, the viability, apoptosis, proliferation, invasion, migration, and DNA damage of the glioma cells were detected by MTT, flow cytometry, colony formation, transwell, wound healing, and γH2AX immunofluorescence assays, respectively. IC50 of HSYA in glioma cells was analyzed by Probit regression analysis. The expressions of MYC, NBS1, factors related to migration, invasion, apoptosis, and DNA damage of the glioma cells were determined by Western blot or RT-qPCR.Results: MYC and NBS1 were high-expressed in glioma, and NBS1 was targeted by MYC. HSYA and siRNA targeting MYC inhibited the cell viability, proliferation, invasion, migration, and induced the cell apoptosis of glioma cells. HSYA upregulated the expressions of MYC, γH2AX, E-Cadherin, Bax, and Cleaved-PARP1, stimulated the activation of NBS1, MRE11, RAD50, and ATM, and downregulated the expressions of N-Cadherin and Bcl2 in glioma cells. SiMYC decreased the IC50 of HSYA in the glioma cells, enhanced the sensitivity of glioma cells to HSYA, and inhibited the activation of NBS1 and ATM. NBS1 overexpression reversed the effect of siRNA targeting MYC on glioma cells.Conclusion: MYC silencing inhibited the DNA damage response via regulation of NBS1, leading to DNA repair deficiency, and subsequently enhanced the sensitivity of glioma cells to HSYA.Keywords: glioma, hydroxysafflor yellow A, MYC, NBS1, drug sensitivity, DNA repair
