J Cancer 2015; 6(7):643-651. doi:10.7150/jca.11913
The Blockage of KCa3.1 Channel Inhibited Proliferation, Migration and Promoted Apoptosis of Human Hepatocellular Carcinoma Cells
1. Department of Laboratory Medicine, Affiliated Fourth Hospital of Harbin Medical University, Harbin 150081, PR China
2. Department of Pharmacology, Harbin Medical University, Harbin 150081, Heilongjiang Province, China
3. Department of Anesthesiology, Affiliated Hospital of Chengde Medical University, Chengde, Hebei Province, China
* contributed equally to this work.
The intermediate conductance calcium-activated potassium channel KCa3.1 plays an important role in regulating cell proliferation and migration. However, the role of KCa3.1 channel in human hepatocellular carcinoma remained unknown. This study was therefore performed to investigate the effects of KCa3.1 potassium channel blocker on the proliferation, apoptosis and migration of human hepatocellular cancer cells HepG2. KCa3.1 mRNA and protein were detected in HepG2. Furthermore, KCa3.1 potassium channel blocker TRAM-34 was capable to inhibit the proliferation and induce the apoptosis of HepG2 cells, which can be partially attenuated by 1-EBIO, an activator of KCa3.1 channel. Moreover, the migration of HepG2 was obviously inhibited by TRAM-34. Consistently, knockdown of KCa3.1 channel using its siRNA was also able to induce apoptosis and suppress proliferation and migration of HepG2. Meanwhile, intracellular ROS level was found augmented in HepG2 treated with TRAM-34. More importantly, p53 protein was found translocation from the cytoplasm into the nuclei of HepG2. Collectively, inhibition of KCa3.1 channel suppressed the growth and migration, and promoted the apoptosis of human hepatocellular carcinoma cells by regulating intracellular ROS level and promoting p53 activation. This data suggests TRAM-34 as a promising anti-tumor drug for liver cancer.
Keywords: TRAM-34, Migration, Apoptosis, Proliferation, p53, ROS
Liu Y, Zhao L, Ma W, Cao X, Chen H, Feng D, Liang J, Yin K, Jiang X. The Blockage of KCa3.1 Channel Inhibited Proliferation, Migration and Promoted Apoptosis of Human Hepatocellular Carcinoma Cells. J Cancer 2015; 6(7):643-651. doi:10.7150/jca.11913. Available from http://www.jcancer.org/v06p0643.htm