Department of Molecular Medicine, Beckman Research Institute, City of Hope Comprehensive Cancer Center, Duarte, CA, USA.
Cancer Res. 2011 May 1;71(9):3182-8. doi: 10.1158/0008-5472.CAN-10-2380. Epub 2011 Apr 26.
Persistent STAT3 signaling contributes to malignant progression in many diverse types of human cancer. STAT3 is constitutively active in activated B-cell (ABC)-like diffuse large B-cell lymphomas (DLBCL), a class of nongerminal center derived DLBCL cells for which existing therapy is weakly effective. In this report, we provide a preclinical proof of concept that STAT3 is an effective molecular target for ABC-like DLBCL therapy. Direct inhibition of STAT3 with short hairpin RNA suppressed the growth of human ABC-like DLBCL in mouse models in a manner associated with apoptosis, repression of STAT3 target genes, and inhibition of a tumor-promoting microenvironment. Together, these results suggest that STAT3 is essential to maintain the pathophysiology of ABC-like DLBCL and therefore that STAT3 inhibition may offer a promising approach in its therapy.
持续的 STAT3 信号转导有助于许多不同类型的人类癌症的恶性进展。STAT3 在激活 B 细胞（ABC）样弥漫性大 B 细胞淋巴瘤（DLBCL）中持续激活，ABC 样 DLBCL 细胞属于非生发中心来源的 DLBCL 细胞，目前的治疗方法对此类肿瘤效果较弱。在本报告中，我们提供了一个临床前概念验证，证明 STAT3 是 ABC 样 DLBCL 治疗的有效分子靶点。用短发夹 RNA 直接抑制 STAT3 以凋亡、抑制 STAT3 靶基因和抑制促进肿瘤的微环境的方式，抑制了 ABC 样 DLBCL 在小鼠模型中的生长。这些结果表明，STAT3 对于维持 ABC 样 DLBCL 的病理生理学至关重要，因此 STAT3 抑制可能是其治疗的一种有前途的方法。
