scholarly journals Gelsolin regulates proliferation, apoptosis and invasion in NK/T-cell lymphoma cells through the PI3K/Akt signaling pathway

2017 ◽  
Author(s):  
Yanwei Guo ◽  
Hongqiao Zhang ◽  
Xin Xing ◽  
Lijuan Wang ◽  
Jian Zhang ◽  
...  

AbstractThe expression of gelsolin (GSN) is abnormal in many cancers, including extranodal nasal-type natural killer/T-cell lymphoma (NKTCL). However, the biological function of GSN and its mechanism in NKTCL remain unclear. We found GSN overexpression significantly suppressed cell proliferation, colony formationand invasion and promoted apoptosis of YTS cells. Moreover, the upregulation of GSN significantly decreased the protein levels of PI3K and p-AKT. Interestingly, blocking the PI3K/AKT signaling pathway significantly inhibited cell proliferation and invasion and promoted apoptosis of YTS cells. In conclusion, our findings indicate that GSN can suppress cell proliferation and invasion and promote apoptosis of YTS cells, which is likely to be mediated at least partially through inhibition of the PI3K/AKT signaling pathway.

2020 ◽  
Vol 40 (10) ◽  
Author(s):  
Gui-Hua Zhang ◽  
Fa-An Miao ◽  
Jin-Ge Xu ◽  
Yan Zhang

Abstract The present study was to determine the roles of Angiotensin (Ang) II in the growth of lymphoma in nude mice and the proliferation and viability of the human Natural Killer/T (NK/T)-cell lymphoma cell line SNK-6, and the activation of downstream signaling pathway. Lymphoma samples and corresponding normal tissues were obtained from lymphoma patients. Proliferation of SNK-6 cells was detected by CCK8 or MTT assay. The levels of Ang II and its receptor Ang II type 1 receptor (AT1R) were higher in lymphoma tissues than those in control tissues. Ang II increased the lymphoma volume and size in nude mice, the proliferation and viability and the proliferating cell nuclear antigen (PCNA) and Ki67 levels of SNK-6 cells. Losartan, an antagonist of AT1R, reduced lymphoma volume and size in nude mice, and the proliferation and viability and the PCNA and Ki67 levels of SNK-6 cells. The levels of phosphorylated phosphatidylinositol 3-kinase (p-PI3K) and phosphorylated protein kinase B (p-Akt) were increased by Ang II and then reduced by losartan in SNK-6 cells. The proliferation and viability of SNK-6 cells were increased by Ang II, but these increases were inhibited by PI3K inhibitor wortmannin and Akt inhibitor MK2206. The increases of PCNA and Ki67 induced by Ang II were inhibited by wortmannin or MK2206 in SNK-6 cells. These results indicate that Ang II/AT1R is activated in lymphoma, and Ang II promotes the progression of lymphoma in nude mice and the proliferation and viability of SNK-6 cells via activating PI3K/Akt signaling pathway.


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Yueqin Feng ◽  
Yuguan Jiang ◽  
Fengjin Hao

Abstract Background Pancreatic cancer is one of the most serious digestive malignancies. At present, there is an extreme lack of effective strategies in clinical treatment. The purpose of this study is to identify key genes and pathways in the development of pancreatic cancer and provide targets for the treatment of pancreatic cancer. Methods GSE15471 and GSE62165 were used to screen differentially expressed genes by GEO2R tool. Hub genes prognostic potential assessed using the GEPIA and Kaplan–Meier plotter databases. The drug susceptibility data of pan-cancer cell lines is provided by The Genomics of Drug Sensitivity in Cancer Project (GDSC). Finally, the effects of PI3K–Akt signaling pathway inhibitors on cell viability of pancreatic cancer cells were detected by cell proliferation and invasion assays. Results A total of 609 differentially expressed genes were screened and enriched in the focal adhesion, phagosome and PI3K–Akt signaling pathway. Of the 15 hub genes we found, four were primarily associated with the PI3K–Akt signaling pathway, including COL3A1, EGF, FN1 and ITGA2. GDSC analysis showed that mTOR inhibitors are very sensitive to pancreatic cancer cells with mutations in EWSR1.FLI1 and RNF43. Cell proliferation and invasion results showed that mTOR inhibitors (GSK2126458) can inhibit the proliferation of pancreatic cancer cells. Conclusions This study suggested that the PI3K–Akt signaling pathway may be a key pathway for pancreatic cancer, our study uncovered the potential therapeutic potential of GSK2126458, a specific mTOR inhibitor, for pancreatic cancer.


Author(s):  
Mi Cheng ◽  
Zequn Liu ◽  
Wanqing Ji ◽  
Jie Zheng ◽  
Huiqian Zeng ◽  
...  

<b><i>Objectives:</i></b> The pathogenesis of preeclampsia (PE) is associated with impaired trophoblast invasion, which results in placental insufficiency. Our earlier studies demonstrated that tissue transglutaminase (tTG) is highly expressed in human PE serum. However, whether tTG participates in trophoblast invasion remains unclear. The aim of the present study was to determine the role and mechanism of tTG in regulating matrix metalloproteinase (MMP)-2/MMP-9 expression to reduce trophoblast invasiveness in PE. <b><i>Methods:</i></b> HTR-8/SVneo cells were transfected with a lentivirus vector and small interfering RNA targeting tTG. The protein level was detected by Western blotting. Cell proliferation and apoptosis were assessed by MTS and flow cytometry assays, respectively. Cell invasion was investigated by Transwell assay. In addition, the influence of tTG on PI3K and AKT mRNA levels in HTR-8/SVneo cells was evaluated using reverse transcription-quantitative PCR. <b><i>Results:</i></b> tTG-overexpression inhibited HTR-8/SVneo cell proliferation and invasion and promoted apoptosis. In addition, upregulation of tTG induced an increase of PI3K and phosphorylated AKT and a decrease of MMP-2 and MMP-9 expression. tTG-knockdown significantly promoted the proliferation and invasion of HTR-8/SVneo cells and inhibited the apoptosis. Furthermore, the PI3K expression level was reduced, and the MMP-2/MMP-9 protein levels were increased. <b><i>Conclusion:</i></b> Taken together, the present study demonstrated that tTG-overexpression inhibited HTR-8/SVneo cell invasion via reducing the expression of MMP-2 and MMP-9 by activating PI3K/AKT signaling pathway, which may lead to the occurrence or development of PE. The present data provide new insights into modulation of tTG expression as a potential therapeutic target for PE.


2012 ◽  
Vol 160 (3) ◽  
pp. 331-342 ◽  
Author(s):  
Kazumi Yoshino ◽  
Kan Kishibe ◽  
Toshihiro Nagato ◽  
Seigo Ueda ◽  
Yuki Komabayashi ◽  
...  

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