Division of Immunotherapy, The Hiram C. Polk, Jr. MD Department of Surgery, Immuno-Oncology Program, Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY 40202, USA.
School of Basic Medical Sciences, Hangzhou Normal University, Hangzhou 310030, China.
Int J Mol Sci. 2023 Sep 4;24(17):13666. doi: 10.3390/ijms241713666.
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.
信号转导子和转录激活因子 3（STAT3），它调节多种致癌过程，已被发现在淋巴瘤中持续激活，这表明其可能成为治疗靶点。在这里，我们构建了一种抗 CD19-N-（4-羧基环己基甲基）马来酰亚胺 N-羟基琥珀酰亚胺酯（SMCC）-鱼精蛋白（CSP）-小干扰 RNA（siRNA）缀合物，并证明 CSP-siRNA 缀合物可以在体外特异性结合正常 B 细胞和 A20 淋巴瘤细胞。它降低了 B 细胞淋巴瘤细胞系（A20、SU-DHL-2 和 OCI-Ly3）中的表达，导致淋巴瘤细胞增殖减少，S 期降低，凋亡增加。使用 A20 可移植淋巴瘤模型，我们发现 CSP-siRNA 缀合物可显著抑制肿瘤生长和重量。在接受 CSP-siRNA 治疗的 A20 荷瘤小鼠中，Ki-67、p-STAT3、STAT3 和血清 IL-6 水平均显著降低。这些发现表明，将 siRNA 特异性靶向 B 细胞淋巴瘤细胞系可显著降低体外和体内的 STAT3 活性并抑制肿瘤进展，提示其在癌症治疗中的潜在应用。
