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      Paeoniflorin suppresses pancreatic cancer cell growth by upregulating HTRA3 expression

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          Abstract

          Paeoniflorin (PF) is an active monoterpene glycoside extracted from Paeonia lactiflora Pall. PF has exhibited antitumor effects in various cancer types. However, the effects of PF in pancreatic cancer are largely unexplored. Here, we showed that PF suppressed growth of pancreatic cancer cell lines Capan-1 and MIAPaCa-2 and profoundly sensitized these cells to X-ray irradiation. Through microarray analysis, we identified HTRA3, a tumor-suppressor candidate gene, as the most increased gene upon PF treatment in Capan-1 cells. Ectopic expression of HTRA3 led to reduced cell proliferation and increased expression of apoptotic protein Bax, suggesting a tumor suppressive role of HTRA3 in pancreatic cancer cells. Together, our results provide a set group of genetic proofs and biological proofs that PF inhibited pancreatic cancer growth by upregulating HTRA3.

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          Most cited references 26

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          FunRich: An open access standalone functional enrichment and interaction network analysis tool.

          As high-throughput techniques including proteomics become more accessible to individual laboratories, there is an urgent need for a user-friendly bioinformatics analysis system. Here, we describe FunRich, an open access, standalone functional enrichment and network analysis tool. FunRich is designed to be used by biologists with minimal or no support from computational and database experts. Using FunRich, users can perform functional enrichment analysis on background databases that are integrated from heterogeneous genomic and proteomic resources (>1.5 million annotations). Besides default human specific FunRich database, users can download data from the UniProt database, which currently supports 20 different taxonomies against which enrichment analysis can be performed. Moreover, the users can build their own custom databases and perform the enrichment analysis irrespective of organism. In addition to proteomics datasets, the custom database allows for the tool to be used for genomics, lipidomics and metabolomics datasets. Thus, FunRich allows for complete database customization and thereby permits for the tool to be exploited as a skeleton for enrichment analysis irrespective of the data type or organism used. FunRich (http://www.funrich.org) is user-friendly and provides graphical representation (Venn, pie charts, bar graphs, column, heatmap and doughnuts) of the data with customizable font, scale and color (publication quality).
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            HtrA serine proteases as potential therapeutic targets in cancer.

            The human HtrA family of serine proteases consists of four members: HtrA1, HtrA2, HtrA3 and HtrA4. Although prokaryotic HtrA proteins are well characterized in their dual roles as chaperones and proteases that degrade misfolded proteins in the periplasm, some members of mammalian HtrA proteins are described as potential modulators of programmed cell death and chemotherapy-induced cytotoxicity. Goal of this review article is to describe the molecular alterations associated with these HtrA serine proteases and how these alterations may be associated with tumor behavior and response to chemotherapy. We will also discuss evidence that chemotherapeutic drugs regulate the expression and activation of HtrA serine proteases and that these proteases contributes to programmed cell death. Finally, we will discuss the potential role of epigenetic therapy in targeting the expression and activation of HtrA serine proteases and the mechanisms by which these proteases enhance cytotoxic effect of conventional chemotherapy.
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              Paeoniflorin inhibits human gastric carcinoma cell proliferation through up-regulation of microRNA-124 and suppression of PI3K/Akt and STAT3 signaling.

              To examine the potential anti-tumor activity of paeoniflorin in the human gastric carcinoma cell line MGC-803.
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                Author and article information

                Journal
                Drug Des Devel Ther
                Drug Des Devel Ther
                Drug Design, Development and Therapy
                Drug Design, Development and Therapy
                Dove Medical Press
                1177-8881
                2017
                23 August 2017
                : 11
                : 2481-2491
                Affiliations
                [1 ]The Third Department of Oncology, The First Affiliated Hospital of Hunan College of Traditional Chinese Medicine, Zhuzhou, Hunan
                [2 ]State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou, Guangdong
                [3 ]Department of Traditional Chinese Medicine, The First Affiliated Hospital of Xian Jiaotong University, Xian, Shanxi, People’s Republic of China
                Author notes
                Correspondence: Debin Zhuo, The First Affiliated Hospital of Hunan College of Traditional Chinese Medicine, 571 Middle People Road, Zhuzhou, Hunan, 412000, People’s Republic of China, Tel +86 152 7330 0259, Fax +86 731 2829 0000, Email 1255057058@ 123456qq.com
                [*]

                These authors contributed equally to this work

                Article
                dddt-11-2481
                10.2147/DDDT.S134518
                5574596
                © 2017 Li et al. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

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