GLI1 inhibitor GANT61 exhibits antitumor efficacy in T-cell lymphoma cells through down-regulation of p-STAT3 and SOCS3.
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.
Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, P.R. China.
Lingyun
L
Geng
Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, P.R. China.
Kang
K
Lu
Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, P.R. China.
Peipei
P
Li
Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, P.R. China.
Xinyu
X
Li
Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, P.R. China.
Xiangxiang
X
Zhou
Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, P.R. China.
Ying
Y
Li
Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, P.R. China.
Xin
X
Wang
D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D020868:Gene Silencing; D006801:Humans; D007150:Immunohistochemistry; D016399:Lymphoma, T-Cell / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011725:Pyridines / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D000071223:Suppressor of Cytokine Signaling 3 Protein / Q000378:metabolism*; D000071676:Zinc Finger Protein GLI1 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism
C551027:GANT 61; C400551:GLI1 protein, human; D011725:Pyridines; D011743:Pyrimidines; D050796:STAT3 Transcription Factor; D000071223:Suppressor of Cytokine Signaling 3 Protein; D000071676:Zinc Finger Protein GLI1
GLI1; STAT3; T-cell lymphoma; signaling pathway; targeted therapy