Effect of MELK Inhibitor OTSSP167 on Diffuse Large B-Cell Lymphoma.
10.19746/j.cnki.issn.1009-2137.2023.03.018
- Author:
Jun-Yi ZHOU
1
;
Hao HUANG
1
;
Yan ZHUANG
1
;
Xiao-Min ZHONG
2
,
3
Author Information
1. The Huaian Clinical College of Xuzhou Medical University, Huai'an 223300, Jiangsu Province, China.
2. The Huaian Clinical College of Xuzhou Medical University, Huai'an 223300, Jiangsu Provinc China.E-mail：13912074971@
3. com.
- Publication Type:Journal Article
- Keywords:
proliferation;
MELK inhibitor;
OTSSP167;
apoptosis;
diffuse large B-cell lymphoma
- MeSH:
Mice;
Animals;
Mice, Nude;
Cell Line, Tumor;
Cell Proliferation;
Caspase 3;
Apoptosis Regulatory Proteins;
Caspases;
Lymphoma, Large B-Cell, Diffuse/pathology*
- From:
Journal of Experimental Hematology
2023;31(3):739-745
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To investigate the effect of MELK inhibitor OTSSP167 against diffuse large B-cell lymphoma (DLBCL).
METHODS:The effect of OTSSP167 on activity, proliferation, and apoptosis of DLBCL cell line (SUDHL2 and HBL1) was detected by CCK-8 assay, 5-ethynyl-2'-deoxyuridine (EdU) staining, and Annexin V-FITC/PI double staining, respectively. DLBCL cells were inoculated into nude mice, after 4 weeks of OTSSP167 treatment, the effect of OTSSP167 on DLBCL growth in vivo was detected. Caspase-GloTM 3/7 enzyme activity assay kit was used to detect the effect of OTSSP167 on Caspase 3/7 enzyme activity of DLBCL cells. The expression levels of apoptosis and cycle-related proteins were detected by Western blot.
RESULTS:OTSSP167 significantly inhibited the activity of SUDHL2 and HBL1 cells in a dose-dependent manner (r =-0.61, r =-0.52). EdU staining showed that OTSSP167 could significantly inhibit the proliferation of SUDHL2 and HBL1 cells. Annexin V-FITC/PI result showed that OTSSP167 could significantly promote the apoptosis of SUDHL2 and HBL1 cells (P <0.001). The result of in vivo experiment showed that OTSSP167 could inhibit the growth of SUDHL2 cells in nude mice. The result of TUNEL staining of tumor further confirmed that OTSSP167 could promote the apoptosis of SUDHL2 cells. Caspase 3/7 enzyme activity test demonstrated that OTSSP167 could significantly increase caspase activity in SUDHL2 and HBL1 cells (r =0.98, r =0.87). Western blot showed that OTSSP167 could dose-dependently inhibit the expression of PARP, Bcl-xL, and Bcl-2 in apoptosis signaling pathway (r =-0.93, r =-0.66, r =-0.87), while p53 protein was significantly up-regulated (r =0.82). The expression of cell cycle-related proteins cdc2, Cyclin E1, Cyclin A2, and Cyclin B1 also showed a dose-dependent down-regulation (r =-0.89, r =-0.83, r =-0.61, r =-0.93).
CONCLUSION:The MELK inhibitor OTSSP167 can inhibit the proliferation and promote the apoptosis of DLBCL cells by inhibiting the expression of cycle-related proteins and anti-apoptosis-related proteins.
