Chloride intracellular channel 1 regulates colon cancer cell migration and invasion through ROS/ERK pathway

AIM: To investigate the mechanisms of chloride intracellular channel 1 (CLIC1) in the metastasis of colon cancer under hypoxia-reoxygenation (H-R) conditions.

Function of chloride intracellular channel 1 in gastric cancer cells

AIM:To investigate the effect of chloride intracellular channel 1(CLIC1) on the cell proliferation,apoptosis,migration and invasion of gastric cancer cells.METHODS:CLIC1 expression was evaluated in human gastric cancer cell lines SGC-7901 and MGC-803 by real time polymerase chain reaction(RT-PCR).Four segments of small interference RNA(siRNA) targeting CLIC1 mRNA and a no-sense control segment were designed by bioinformatics technology.CLIC1 siRNA was selected using Lipofectamine 2000 and transfected transiently into human gastric cancer SGC-7901 and MGC-803 cells.The transfected efficiency was observed under fluorescence microscope.After transfection,mRNA expression of CLIC1 was detected with RT-PCR and Western blotting was used to detect the protein expression.Proliferation was examined by methyl thiazolyl tetrazolium and apoptosis was detected with flow cytometry.Polycarbonate membrane transwell chamber and Matrigel were used for the detection of the changes of invasion and migration of the two cell lines.RESULTS:In gastric cancer cell lines SGC-7901 and MGC-803,CLIC1 was obviously expressed and CLIC1 siRNA could effectively suppress the expression of CLIC1 protein and mRNA.Proliferation of cells transfected with CLIC1 siRNA3 was enhanced notably,and the highest proliferation rate was 23.3%(P = 0.002) in SGC-7901 and 35.55%(P = 0.001) in MGC-803 cells at 48 h.The G2/M phase proportion increased,while G0/G1 and S phase proportions decreased.The apoptotic rate of the CLIC1 siRNA3 group obviously decreased in both SGC-7901 cells(62.24%,P = 0.000) and MGC-803 cells(52.67%,P = 0.004).Down-regulation of CLIC1 led to the inhibition of invasion and migration by 54.31%(P = 0.000) and 33.62%(P = 0.001) in SGC-7901 and 40.74%(P = 0.000) and 29.26%(P = 0.002) in MGC-803.However,there was no significant difference between the mock group cells and the negative control group cells.

Cellular physiological approach for treatment of gastric cancer

Recent studies show that ion channels/transporters play important roles in fundamental cellular functions that would be involved in the cancer process. We review the evidence for their expression and functioning in human gastric cancer (GC), and evaluate the potential of cellular physiological approach in clinical management. Various types of ion channels, such as voltage-gated K+ channels, intracellular Cl- channels and transient receptor potential channels have been found to express in GC cells and tissues, and to control cell cycles. With regard to water channels, aquaporin 3 and 5 play an important role in the progression of GC. Regulators of intracellular pH, such as anion exchanger, sodium-hydrogen exchanger, vacuolar H+-ATPases and carbonic anhydrases are also involved in tumorigenesis of GC. Their pharmacological manipulation and gene silencing affect cellular behaviours, suggesting their potential as therapeutic targets for GC. Our studies indicate the intracellular Cl- concentration could act as a mediator of cellular signaling and control cell cycle progression in GC cells. Further, we demonstrate the cytocidal effects of hypotonic shock on GC cells, and indicate that the blockade of Cl- channels/transporters enhances these effects by inhibiting regulatory volume decrease. A deeper understanding of molecular mechanisms may lead to the discovery of these cellular physiological approaches as a novel therapeutic strategy for GC.

NKCC1 and NKCC2:The pathogenetic role of cation-chloride cotransporters in hypertension

This review summarizes the data on the functional significance of ubiquitous(NKCC1)and renal-specific(NKCC2)isoforms of electroneutral sodium,potassium and chloride cotransporters.These carriers contribute to the pathogenesis of hypertension via regulation of intracellular chloride concentration in vascular smooth muscle and neuronal cells and via sensing chloride concentration in the renal tubular fluid,respectively.Both NKCC1 and NKCC2 are inhibited by furosemide and other high-ceiling diuretics widely used for attenuation of extracellular fluid volume.However,the chronic usage of these compounds for the treatment of hypertension and other volume-expanded disorders may have diverse side-effects due to suppression of myogenic response in microcirculatory beds.