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

The signal transducer and activator of transcription 3 (), 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)- small interfering RNA (siRNA) conjugate and demonstrated that the CSP- siRNA conjugate could specifically bind to normal B cells and A20 lymphoma cells in vitro. It decreased the 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- 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- siRNA. These findings indicate that specifically targeting siRNA to B cell lymphoma cell lines can significantly decrease activity and inhibit tumor progression in vitro and in vivo, suggesting its potential utilization for cancer treatment.