title: Suppression of PRKAR1A expression enhances anti-proliferative and apoptotic effects of protein kinase inhibitors and chemotherapeutic drugs on cholangiocarcinoma cells.
abstract: Suppression of protein kinase A regulatory subunit 1 alpha (PRKAR1A) has been proven to inhibit cholangiocarcinoma (CCA) cell growth and enhance apoptosis. In the present study, we aimed to determine synergistic and/or additive effects of chemotherapeutic agents, including protein kinase inhibitors (i.e. sorafenib, sunitinib, gefitinib, Met inhibitor) and conventional chemotherapeutic drugs (i.e. 5-fluorouracil, doxorubicin, paclitaxel, gemcitabine), in PRKARIA knockdown CCA cell lines. The results revealed that PRKAR1A suppressed CCA cell lines demonstrated enhanced sensitivity to some chemotherapeutic drugs when compared to control cells. Moreover, PRKAR1A knockdown in combination with either sorafenib or 5-fluorouracil increased apoptotic effects on CCA cell lines. Therefore, selective inhibition of PRKAR1A appears to enhance the growth inhibitory effects of chemotherapeutic drugs as well as induce apoptotic cell death. Our findings suggest that additional suppression of PRKAR1A expression may increase the efficacy of conventional CCA chemotherapeutic treatment. Clinical studies in CCA patients now need to be conducted.
authors.affiliation: Department of Biochemistry, Khon Kaen University, Khon Kaen, Thailand. watloi@yahoo.com
authors.forename: Watcharin
authors.initials: W
authors.lastname: Loilome
authors.forename: Sirinun
authors.initials: S
authors.lastname: Juntana
authors.forename: Chadamas
authors.initials: C
authors.lastname: Pinitsoontorn
authors.forename: Nisana
authors.initials: N
authors.lastname: Namwat
authors.forename: Wichittra
authors.initials: W
authors.lastname: Tassaneeyakul
authors.forename: Puangrat
authors.initials: P
authors.lastname: Yongvanit
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001650:Bile Duct Neoplasms; D001653:Bile Ducts, Intrahepatic; D045744:Cell Line, Tumor; D018281:Cholangiocarcinoma; D017868:Cyclic AMP-Dependent Protein Kinases; D006801:Humans; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use
chemical_list: D047428:Protein Kinase Inhibitors; D017868:Cyclic AMP-Dependent Protein Kinases