Growth of T-cell lymphoma cells is inhibited by mPGES-1/PGE2 suppression via JAK/STAT, TGF-β/Smad3 and PI3K/AKT signal pathways

  • Transl Cancer Res. 2022 Jul;11(7):2175-2184. doi: 10.21037/tcr-21-2834.
Yiqing Li  #  1  2 ,  Meng Qiu  #  1  2  3 ,  Boqi Li  1  2 ,  Jie Xiao  1  2 ,  Wenjuan Yang  1  2 ,  Shuangfeng Xie  1  2 ,  Yumo Du  2  4 ,  Kezhi Huang  1  2 ,  Danian Nie  1  2
Affiliations
  • 1. Department of Hematology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
  • 2. Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
  • 3. The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China.
  • 4. Department of Respirology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
  • # Contributed equally.
PMID: 35966330 DOI: 10.21037/tcr-21-2834
Abstract

Background: T-cell lymphoma (TCL) has a very poor prognosis with limited treatment options and novel therapeutic target is urgently needed. Our previous studies have found that suppression of membrane-bound prostaglandin E2 synthase l/prostaglandin E2 (mPGES-1/PGE2) exerted anti-neoplastic effects in leukemia cells by suppressing Akt signal pathway. Here, we aim at evaluating the role and mechanism of mPGES-1/PGE2 signaling in TCL.

Methods: Expression of mPGES-1 in TCL cell line Hut78 was analyzed by Western blot and immunofluorescence. CAY10526, a selective mPGES-1 inhibitor, was used to treat Hut 78 cells. Cell viability assays was performed by using cell counting kit-8 (CCK-8). Cell Apoptosis rate was examined by flow cytometer. PGE2 synthesis was detected by enzyme Immunoassay (EIA). The expression of mPGES-1, cleaved Caspase-3, Janus kinase/signal transduction and transcription (JAK/STAT), transforming growth factor-β (TGF-β)/SMAD3 and phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway of Hut 78 cells after exposed to CAY10526 was analyzed by Western blot.

Results: mPGES-1 was highly expressed in Hut78 cell compared to normal peripheral blood mono-nuclear cells. CAY10526 inhibited cell proliferation and induced Apoptosis in Hut78 cells. These effects may be partially attributed to the activation of the Caspase family and the inhibition of JAK/STAT, TGF-β/SMAD3 and PI3K/Akt signal pathways.

Conclusions: Our results suggested that mPGES-1/PGE2 could be a potential therapeutic target for TCL.

Keywords
Janus kinase/signal transduction and transcription (JAK/STAT); T-cell lymphoma (TCL); mPGES-1/PGE2; phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT); transforming growth factor-β (TGF-β)/Smad3.
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