Specific Targeting of STAT3 in B Cells Suppresses Progression of B Cell Lymphoma

The signal transducer and activator of transcription 3 (STAT3), which regulates multiple oncogenic processes, has been found to be constitutively activated in lymphoma, suggesting its potential as a therapeutic target. Here, we constructed an anti-CD19-N-(4-carboxycyclohexylmethyl) maleimide N-hydro...

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Bibliographic Details
Published in:International journal of molecular sciences 2023-09, Vol.24 (17), p.13666
Main Authors: Wang, Lipei, Zhou, Mingqian, Kong, Xiangyu, Wu, Shouzhen, Ding, Chuanlin, Hu, Xiaoling, Guo, Haixun, Yan, Jun
Format: Article
Language:English
Subjects:
Analysis
Antigens
Apoptosis
B cells
Cell cycle
Cell growth
conjugate
Development and progression
Health aspects
Kinases
Lymphoma
Medical prognosis
Non-Hodgkin's lymphomas
siRNA
SMCC
STAT3
Transcription factors
Tumors
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Summary:The signal transducer and activator of transcription 3 (STAT3), which regulates multiple oncogenic processes, has been found to be constitutively activated in lymphoma, suggesting its potential as a therapeutic target. Here, we constructed an anti-CD19-N-(4-carboxycyclohexylmethyl) maleimide N-hydroxysuccinimide ester (SMCC)-protamine (CSP)-STAT3 small interfering RNA (siRNA) conjugate and demonstrated that the CSP-STAT3 siRNA conjugate could specifically bind to normal B cells and A20 lymphoma cells in vitro. It decreased the STAT3 expression in B cell lymphoma cell lines (A20, SU-DHL-2 and OCI-Ly3), resulting in reduced proliferation of lymphoma cells featured with lower S-phase and higher apoptosis. Using an A20 transplantable lymphoma model, we found that the CSP-STAT3 siRNA conjugate significantly inhibited tumor growth and weight. Ki-67, p-STAT3, STAT3, and serum IL-6 levels were all significantly reduced in A20-bearing mice treated with CSP-STAT3 siRNA. These findings indicate that specifically targeting STAT3 siRNA to B cell lymphoma cell lines can significantly decrease STAT3 activity and inhibit tumor progression in vitro and in vivo, suggesting its potential utilization for cancer treatment.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms241713666