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10.12659/msm.901667 http://scihub22266oqcxt.onion/10.12659/msm.901667 C5266205!5266205 !28090074     free     free     free Deprecated: Implicit conversion from float 217.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 217.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 217.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 217.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 217.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 217.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 217.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 217.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 251.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 251.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 251.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\28090074 .jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117       Med+Sci+Monit 2017 ; 23 (ä): 266-275 Nephropedia Template TP {{tp|p=28090074 |t=2017. Targeting of Wnt/?-Catenin by Anthelmintic Drug Pyrvinium Enhances Sensitivity of Ovarian Cancer Cells to Chemotherapy |pdf=|usr=}}{{28090074 }} gab.com Text Targeting of Wnt/ -Catenin by Anthelmintic Drug Pyrvinium Enhances Sensitivity of Ovarian Cancer Cells to Chemotherapy JO: Med Sci Monit http://www.kidney.de/pget.php?&tw=1&pmid=28090074 #FOAvip BACKGROUND Aberrant activation of Wnt/?-catenin has been shown to promote ovarian cancer proliferation and chemoresistance. Pyrvinium, an FDA-approved anthelmintic drug, has been identified as a potent Wnt inhibitor. Pyrvinium may sensitize ovarian cancer cells to chemotherapy. MATERIAL AND METHODS The effect of pyrvinium alone and its combination with paclitaxel in ovarian cancer was investigated using an in vitro culture system and in vivo xenograft models. The mechanisms of its action were also analyzed, focusing on the Wnt/?-catenin pathway. RESULTS Pyrvinium inhibited growth and induced apoptosis of paclitaxel- and cisplatin-resistant epithelial ovarian cancer cell lines A2278/PTX and SK-OV-3. Its combination with paclitaxel was synergistic in targeting ovarian cancer cells in vitro. In 3 independent ovarian xenograft mouse models, pyrvinium alone inhibited tumor growth. More importantly, we observed significant inhibition of tumor growth throughout the treatment when using pyrvinium and paclitaxel combined. Mechanistically, pyrvinium increased the Wnt-negative regulator axin and decreased the b-catenin levels in ovarian cancer cells. In addition, pyrvinium suppressed Wnt/b-catenin-mediated transcription, as shown by the decreased mRNA levels of MYC, cyclin D, and BCL-9. In contrast, the inhibitory effects of pyrvinium were reversed by ?-catenin stabilization or overexpression, demonstrating that pyrvinium acted on ovarian cancer cells via targeting the Wnt/?-catenin signaling pathway. CONCLUSIONS We demonstrated that the anthelmintic drug pyrvinium targets ovarian cancer cells through suppressing Wnt/?-catenin signaling. Our work highlights the therapeutic value of inhibiting Wnt/?-catenin in ovarian cancer. Twit Text FOAVip Targeting of Wnt/ -Catenin by Anthelmintic Drug Pyrvinium Enhances Sensitivity of Ovarian Cancer Cells to Chemotherapy ????Med Sci Monit http://www.kidney.de/pget.php?&tw=1&pmid=28090074 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=28090074 #FOAvip English Wikipedia <ref>{{Cite pmid|28090074 }}</ref> Targeting of Wnt/?-Catenin by Anthelmintic Drug Pyrvinium Enhances Sensitivity of Ovarian Cancer Cells to Chemotherapy #MMPMID28090074 Zhang C ; Zhang Z ; Zhang S ; Wang W ; Hu P Med Sci Monit 2017[Jan]; 23 (ä): 266-275 PMID28090074 show ga BACKGROUND Aberrant activation of Wnt/?-catenin has been shown to promote ovarian cancer proliferation and chemoresistance. Pyrvinium, an FDA-approved anthelmintic drug, has been identified as a potent Wnt inhibitor. Pyrvinium may sensitize ovarian cancer cells to chemotherapy. MATERIAL AND METHODS The effect of pyrvinium alone and its combination with paclitaxel in ovarian cancer was investigated using an in vitro culture system and in vivo xenograft models. The mechanisms of its action were also analyzed, focusing on the Wnt/?-catenin pathway. RESULTS Pyrvinium inhibited growth and induced apoptosis of paclitaxel- and cisplatin-resistant epithelial ovarian cancer cell lines A2278/PTX and SK-OV-3. Its combination with paclitaxel was synergistic in targeting ovarian cancer cells in vitro. In 3 independent ovarian xenograft mouse models, pyrvinium alone inhibited tumor growth. More importantly, we observed significant inhibition of tumor growth throughout the treatment when using pyrvinium and paclitaxel combined. Mechanistically, pyrvinium increased the Wnt-negative regulator axin and decreased the b-catenin levels in ovarian cancer cells. In addition, pyrvinium suppressed Wnt/b-catenin-mediated transcription, as shown by the decreased mRNA levels of MYC, cyclin D, and BCL-9. In contrast, the inhibitory effects of pyrvinium were reversed by ?-catenin stabilization or overexpression, demonstrating that pyrvinium acted on ovarian cancer cells via targeting the Wnt/?-catenin signaling pathway. CONCLUSIONS We demonstrated that the anthelmintic drug pyrvinium targets ovarian cancer cells through suppressing Wnt/?-catenin signaling. Our work highlights the therapeutic value of inhibiting Wnt/?-catenin in ovarian cancer. |Animals [MESH] |Anthelmintics/*pharmacology [MESH] |Antineoplastic Agents/pharmacology/*therapeutic use [MESH] |Apoptosis/drug effects [MESH] |Cell Line, Tumor [MESH] |Cell Proliferation/drug effects [MESH] |Drug Resistance, Neoplasm/drug effects [MESH] |Drug Synergism [MESH] |Female [MESH] |Humans [MESH] |Lithium Chloride/pharmacology [MESH] |Mice, SCID [MESH] |Ovarian Neoplasms/*drug therapy/*pathology [MESH] |Paclitaxel/pharmacology [MESH] |Pyrvinium Compounds/*pharmacology [MESH] |Wnt Signaling Pathway/*drug effects [MESH]Targeting of Wnt/?-Catenin by Anthelmintic Drug Pyrvinium Enhances Sen(epmc).pdf DeepDyve Pubget Overpricing