Catechol‐O‐methyltransferase, a new target for pancreatic cancer therapy. Issue 5 (25th March 2015)

• Record Type: Journal Article
• Authors: Wu, Wenming; Wu, Qiao; Hong, Xiafei; Zhou, Li; Zhang, Jie; You, Lei; Wang, Wenze; Wu, Huanwen; Dai, Hongmei; Zhao, Yupei
• Is Part Of: Cancer science. Volume 106:Issue 5(2015:May)
• Page Start: 576
• Page End: 583
• Publication Date: 2015-03-25
• Subjects: Cancer -- Periodicals; Neoplasms -- Periodicals; Research -- Periodicals; Electronic journals; 616.994005
• DOI: 10.1111/cas.12648
• Languages: English
• ISSNs: 1347-9032

Abstract

<abstract abstract-type="main" id="cas12648-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <p>Catechol‐<italic>O</italic>‐methyltransferase (COMT) is an important molecule in different types of cancers. Its biological effect and therapeutic significance, however, rarely been investigated fully in pancreatic cancer. Immunohistologically, high COMT expression was significantly correlated with the longer overall survival of patients (<italic>P </italic>< 0.05), indicating its protective nature. The effects of COMT on cell growth, apoptosis, and invasion were evaluated using overexpression and silencing methods. In detail, we carried out experiments using one stably transduced and two transiently transfected pancreatic cancer cell lines <italic>in vitro</italic>, and one stably transduced cell line <italic>in vivo</italic> mice xenograft models. <italic>In vitro</italic> experiments showed that COMT inhibited cell proliferation, enhanced gemcitabine‐induced apoptosis, and inhibited cell invasion in stably transduced and transiently transfected cell lines by regulating the PI3K/Akt pathway, p53, and E‐cadherin. The COMT overexpressed and silenced cell lines showed significantly inhibited and enhanced growth capacities in <italic>in vivo</italic> xenograft models, respectively. In conclusion, COMT suppressed pancreatic cancer and its high expression predicted longer survival time. The interaction of COMT with the PI3K/Akt pathway makes it a potential target for therapy.</p> </abstract>