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

Yiqing Li; Meng Qiu; Boqi Li; Jie Xiao; Wenjuan Yang; Shuangfeng Xie; Yumo Du; Kezhi Huang; Danian Nie

doi:10.21037/tcr-21-2834

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.

Authors

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.

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.