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.