title: WP1066 exhibits antitumor efficacy in nasal‑type natural killer/T-cell lymphoma cells through downregulation of the STAT3 signaling pathway.
abstract: Nasal-type natural killer/T-cell lymphoma (nasal NKTCL) is an aggressive hematological neoplasm with poor prognosis, and its incidence is higher in Asia than in Western countries. Increasing evidence suggests that aberrant activation of signal transducers and activators of transcription 3 (STAT3) is related to numerous malignancies. However, the involvement of STAT3 in the pathogenesis of nasal NKTCL is poorly understood. In this study, immunohistochemistry (IHC) showed that 21/28 (75.0%) nasal NKTCL tissues harbored constitutively expression of phospho‑STAT3 (p‑STAT3) which was positively correlated with the Ki‑67 levels (P﹤0.05). Immunofluorescence (IF) also detected p‑STAT3 expression in SNK6 cells (NKTCL cell line). Furthermore, WP1066 (a novel selective STAT3 inhibitor) was able to inhibit proliferation and induce apoptosis of SNK6 cells. Moreover, western blot analysis and RT‑PCR demonstrated that WP1066 downregulated the protein and mRNA expressions of the pro‑survival molecules (including c‑Myc, cyclin D1, and Bcl‑2) in SNK6 cells. These results suggested that STAT3 activation represents a potential target in nasal NKTCL. WP1066 may be a promising agent in antitumor therapy against nasal NKTCL.
authors.affiliation: Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China.
authors.forename: Lingyun
authors.initials: L
authors.lastname: Geng
authors.affiliation: Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China.
authors.forename: Xinyu
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China.
authors.forename: Xiangxiang
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China.
authors.forename: Xiaosheng
authors.initials: X
authors.lastname: Fang
authors.affiliation: Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China.
authors.forename: Dai
authors.initials: D
authors.lastname: Yuan
authors.affiliation: Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D016399:Lymphoma, T-Cell / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D055611:Natural Killer T-Cells / Q000187:drug effects / Q000473:pathology; D009669:Nose Neoplasms / Q000188:drug therapy* / Q000473:pathology; D011725:Pyridines / Q000008:administration & dosage*; D050796:STAT3 Transcription Factor / Q000096:biosynthesis* / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D020032:Tyrphostins / Q000008:administration & dosage*
chemical_list: D011725:Pyridines; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D020032:Tyrphostins; C519885:WP1066