J Cancer 2017; 8(9):1568-1578. doi:10.7150/jca.18697
KCa3.1 as an Effective Target for Inhibition of Growth and Progression of Intrahepatic Cholangiocarcinoma
1. Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China;
2. Collaborative Innovation Center for Diagnosis Treatment of Infectious Diseases, Hangzhou 310003, China;
3. Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou 310029, China;
4. Department of Gastroenterology, Affiliated Hospital of Zunyi Medical College, Zunyi 563003, China.
* These authors contributed equally to this work
Background: Intrahepatic cholangiocarcinoma (ICC) is a high malignant tumor arising from the bile ducts in the liver with a poor prognosis. As current molecular targeted therapies and systemic chemotherapies had limited success in ICC, novel therapeutic targets are needed. In this study, we attempted to investigate the expression and the role of the intermediate conductance calcium-activated potassium channel (KCa3.1) in ICC.
Methods: The expression levels of KCa3.1 channel were measured in 81 resected ICC tumor specimens and the clinicopathological significance of these levels were determined. KCa3.1 channel inhibitor and siRNA were used to study the role of KCa3.1 in proliferation, migration, and invasion of ICC cell lines. The effect of KCa3.1 channel blockade on tumor growth in vivo was also studied using xenograft model in nude mice.
Results: The protein expression of KCa3.1 channel was upregulated in ICC tissues and was correlated with age, lymph node metastasis and TNM stage. And high KCa3.1 expression indicated a worse prognosis in ICC patients. Blocking KCa3.1 channel with a specific inhibitor TRAM-34 reduced the proliferation and invasion of ICC cells. Knockdown of KCa3.1 could achieve the same effects through decreasing NF-κB activation. Further in vivo studies demonstrated that KCa3.1 channel blockade suppressed ICC tumor growth.
Conclusions: Our observations suggested KCa3.1 might be a promising novel therapeutic target in intrahepatic cholangiocarcinoma.
Keywords: KCa3.1, Intrahepatic cholangiocarcinoma, Proliferation, Invasion, TRAM-34.
Song P, Du Y, Song W, Chen H, Xuan Z, Zhao L, Chen J, Chen J, Guo D, Jin C, Zhao Y, Tuo B, Zheng S. KCa3.1 as an Effective Target for Inhibition of Growth and Progression of Intrahepatic Cholangiocarcinoma. J Cancer 2017; 8(9):1568-1578. doi:10.7150/jca.18697. Available from http://www.jcancer.org/v08p1568.htm