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http://ir.nhri.org.tw/handle/3990099045/13490
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| Title: | NBM-BMX, an HDAC8 inhibitor, overcomes temozolomide resistance in glioblastoma multiforme by downregulating the beta-Cateninic-Myc/SOX2 pathway and upregulating p53-mediated MGMT inhibition |
| Other Titles: | NBM-BMX, an HDAC8 Inhibitor, Overcomes Temozolomide Resistance in Glioblastoma Multiforme by Downregulating the β-Catenin/c-Myc/SOX2 Pathway and Upregulating p53-Mediated MGMT Inhibition |
| Authors: | Tsai, CY;Ko, HJ;Chiou, SJ;Lai, YL;Hou, CC;Javaria, T;Huang, ZY;Cheng, TS;Hsu, TI;Chuang, JY;Kwan, AL;Chuang, TH;Huang, CYF;Loh, JK;Hong, YR |
| Contributors: | NHRI Graduate Student Program;Immunology Research Center |
| Abstract: | Although histone deacetylase 8 (HDAC8) plays a role in glioblastoma multiforme (GBM), whether its inhibition facilitates the treatment of temozolomide (TMZ)-resistant GBM (GBM-R) remains unclear. By assessing the gene expression profiles from short hairpin RNA of HDAC8 in the new version of Connectivity Map (CLUE) and cells treated by NBM-BMX (BMX)-, an HDAC8 inhibitor, data analysis reveals that the Wnt signaling pathway and apoptosis might be the underlying mechanisms in BMX-elicited treatment. This study evaluated the efficacy of cotreatment with BMX and TMZ in GBM-R cells. We observed that cotreatment with BMX and TMZ could overcome resistance in GBM-R cells and inhibit cell viability, markedly inhibit cell proliferation, and then induce cell cycle arrest and apoptosis. In addition, the expression level of beta-catenin was reversed by proteasome inhibitor via the beta-catenin/GSK3 beta signaling pathway to reduce the expression level of c-Myc and cyclin D1 in GBM-R cells. BMX and TMZ cotreatment also upregulated WT-p53 mediated MGMT inhibition, thereby triggering the activation of caspase-3 and eventually leading to apoptosis in GBM-R cells. Moreover, BMX and TMZ attenuated the expression of CD133, CD44, and SOX2 in GBM-R cells. In conclusion, BMX overcomes TMZ resistance by enhancing TMZ-mediated cytotoxic effect by downregulating the beta-catenin/c-Myc/SOX2 signaling pathway and upregulating WT-p53 mediated MGMT inhibition. These findings indicate a promising drug combination for precision personal treating of TMZ-resistant WT-p53 GBM cells. |
| Date: | 2021-05-31 |
| Relation: | International Journal of Molecular Sciences. 2021 May 31;22(11):Article number 5907. |
| Link to: | http://dx.doi.org/10.3390/ijms22115907 |
| JIF/Ranking 2023: | http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1422-0067&DestApp=IC2JCR |
| Cited Times(WOS): | https://www.webofscience.com/wos/woscc/full-record/WOS:000660190300001 |
| Cited Times(Scopus): | https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85106917363 |
| Appears in Collections: | [其他] 期刊論文
[莊宗顯] 期刊論文
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| ISI000660190300001.pdf | | 5461Kb | Adobe PDF | 213 | View/Open |
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