GLI1 inhibitor GANT61 exhibits antitumor efficacy in T-cell lymphoma cells through down-regulation of p-STAT3 and SOCS3

// Lingyun Geng 1 , Kang Lu 1 , Peipei Li 1 , Xinyu Li 1 , Xiangxiang Zhou 1 , Ying Li 1 and Xin Wang 1 1 Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, P.R. China Correspondence to: Xin Wang, email: xinw@sdu.edu.cn , xinw007@126.com Keywords: T-cell lymphoma, GLI1, STAT3, signaling pathway, targeted therapy Received: December 20, 2015 Accepted: May 04, 2016 Published: June 02, 2016 ABSTRACT T-cell lymphomas are lymphoid malignancies with aggressive clinical course and poor prognosis. Increasing evidences suggest that deregulation of signal transducer and activator of transcription-3 (STAT3) and suppressor of cytokine signaling 3 (SOCS3) is associated with the pathogenesis of T-cell lymphomas. The hedgehog (Hh)/glioma-associated oncogene-1 (GLI1) pathway, aberrantly activated in a number of tumors, has also been extensively studied. We found that protein expressions of GL11, p-STAT3, STAT3, and SOCS3 were up-regulated in T-cell lymphoma tissues and cell lines. Moreover, the protein expressions of p-STAT3 and SOCS3 were positively correlated with GLI1 in T-cell lymphomas. GLI1 inhibitor GANT61 and lentivirus-mediated siGLI1 exhibited inhibitory effects in the three T-cell lines (Jurkat, Karpass299 and Myla3676 cells). The protein expressions of p-STAT3 and SOCS3 were decreased accompanied with the inhibition of GLI1. These findings indicated that GANT61 is a promising agent against T-cell lymphoma and the antitumor activity might be partly mediated by down-regulating p-STAT3 and SOCS3.