Effect of FTO and inhibitor on rituximab resistance in DLBCL
10.19405/j.cnki.issn1000-1492.2023.05.010
- Author:
Jiwei Gu
1
,
2
;
Mei Shi
2
;
Guoqi Song
1
,
2
Author Information
1. Medical School of Nantong University, Nantong 226001
2. Dept ofHaematology,Afiliated Hospital of Nantong University, Nantong 226001
- Publication Type:Journal Article
- Keywords:
diffuse large B ⁃cell lymphoma;
rituximab;
FTO;
c⁃Myc
- From:
Acta Universitatis Medicinalis Anhui
2023;58(5):760-765
- CountryChina
- Language:Chinese
-
Abstract:
Objective :To explore the effect of FTO(fat mass and obesity⁃associated protein) and inhibitor on rituximab resistance in DLBCL(diffuse large B cell lymphoma) .
Methods :Two cell lines derived from “ double strike ” lymphoma were selected , activated B ⁃cell⁃like ( ABC) OCI⁃LY8 ( LY8) and germinal center B ⁃cell⁃like ( GCB) OCI⁃LY18 (LY18) , and rituximab⁃resistant DLBCL cell lines (LY8R and LY18R) were constructed by “ concentration gradient dosing method ” . The CCK⁃8 method was used to detect the cell survival rate of different concentrations of rituximab after interfering with the parental and drug⁃resistant cells , and the half maximal inhibitory concentration(IC50 ) was calculated ; AnnexinⅤ/PI double staining method was used to detect the apoptotic rate of parent cells and drug⁃resistant cells ; qRT⁃RCR , immunofluorescence and Western blot were used to detect the expression of demethylase FTO in rituximab⁃resistant cells . The expression of FTO was inhibited by adding meclofenamic acid (MA) to drug⁃resistant cell lines , and the inhibition was verified by RT⁃qRCR and Western blot . The expression of c⁃Myc and CEBPA in drug⁃resistant strains after inhibiting FTO was detected by using Western blot .
Results:Compared with the parent cells , the expression of demethylase FTO and c⁃Myc increased , and the expression of CEBPA decreased in the rituximab⁃resistant cell lines , with statistical significance (P < 0. 01) . After the drug⁃resistant cell lines treated with MA , the expression of FTO and c⁃Myc decreased and CEBPA increased , all with statistically significant differences (P < 0. 01) .
Conclusion:The expression of FTO in drug⁃resistant DLBCL significantly increases , and MA inhibits the expression of FTO in drug⁃resistant cells , which may have therapeutic potential for rituximab⁃resistant DLBCL.
- Full text:2024081210203706087FTO及其抑制剂对DLBCL利妥昔单抗耐药的影响_顾季炜.pdf
