Cystic fibrosis (CF) transmembrane conductance regulator (CFTR) is expressed in the epithelial cells of a wide range of organs/tissues from which most cancers are derived. Although accumulating reports have indicated the association of cancer incidence with genetic variations in CFTR gene, the exact role of CFTR in cancer development and the possible underlying mechanism have not been elucidated. Here, we report that CFTR expression is significantly decreased in both prostate cancer cell lines and human prostate cancer tissue samples. Overexpression of CFTR in prostate cancer cell lines suppresses tumor progression (cell growth, adhesion and migration), whereas knockdown of CFTR leads to enhanced malignancies both in vitro and in vivo. In addition, we demonstrate that CFTR knockdown-enhanced cell proliferation, cell invasion and migration are significantly reversed by antibodies against either urokinase plasminogen activator (uPA) or uPA receptor (uPAR), which are known to be involved in various malignant traits of cancer development. More interestingly, overexpression of CFTR suppresses uPA by upregulating the recently described tumor suppressor microRNA-193b (miR-193b), and overexpression of pre-miR-193b significantly reverses CFTR knockdown-enhanced malignant phenotype and abrogates elevated uPA activity in prostate cancer cell line. Finally, we show that CFTR gene transfer results in significant tumor repression in prostate cancer xenografts in vivo. Taken together, the present study has demonstrated a previously undefined tumor-suppressing role of CFTR and its involvement in regulation of miR-193b in prostate cancer development.

Bak Foong Pills (BFP, also known as Bai Feng Wan)is an over-the-counter traditional Chinese medicine (China registration No. Z980035) that has long been used for treating gynecological disorders and improving of overall body functions, including gastrointestinal (GI) function [1]. However, the cellular signaling mechanism underlying BFP action, especially on the GI tract, has not been elucidated.Secretagogue-induced Cl Ϫ secretion by the GI tract is important because Cl Ϫ secretion provides an essential driving force for the lubrication of intestinal contents during regular bowl movements or the flushing of microbial organisms or artificial irritants in host defense responses [2,3]. Epithelial Cl Ϫ channels, especially the cAMP-activated Cl Ϫ channels, play an important role in regulating and maintaining the normal physiological functions of the GI tract. The abnormal regulation of Cl Ϫ channels, such as by cholera toxin, Abstract: Bak Foong Pills (BFP, also known as Bai Feng Wan) is an over-the-counter traditional Chinese medicine that has long been used for treating gynecological disorders and improving overall body functions, including gastrointestinal (GI) function. However, the cellular signaling mechanism underlying BFP action, especially on the GI tract, has not been elucidated. In the present study, the human colonic epithelia cell line T 84 was used as a model to investigate the effect of BFP ethanol extract on ion transport in conjunction with the short-circuit current (I SC ) technique. The results showed that the apical addition of BFP extract produced a concentration-dependent (10-1,000 g/ml, EC 50 ϭ120 g/ml) increase in I SC . The maximal response was observed at 500 g/ml with an increase in I SC of 24.4Ϯ2.3 A/cm 2 and apical conductance. The BFP-induced I SC was not observed when extracellular Cl Ϫ was replaced or when treated with Bumetanide (100 M), an inhibitor of the NaϪ cotransporter. The BFP-induced I SC was insensitive to the Na ϩ channel blocker, amiloride, but partially inhibited by the Cl Ϫ channel blocker, DIDS (100 M), and completely blocked by DPC (2 mM) or glibenclamide (1 mM) with a significant reduction in the apical conductance. The BFP-induced I SC could be mimicked by forskolin (10 M), but inhibited by a pretreatment of the cells with adenylate cyclase inhibitor, MDL-12330A (10 M). Pretreatment with EGTA (5 mM) and thapsigargin (10 M) decreased the BFP-induced I SC by 10%. These results demonstrated that BFP ethanol extract exerted a stimulatory effect on gastrointestinal Cl Ϫ secretion by predominantly activating adenylate cyclase and apical cAMP-dependent Cl Ϫ channels, with minor contributions from calcium-dependent Cl Ϫ channels. The effect of BFP may be explored to treat GI disorders such as constipation.

Peyer's patch lymphocytes may modulate intestinal epithelial barrier and ion transport function in homeostasis and host defense via cell-cell contact and cytokine signaling.

TMP may stimulate cAMP-dependent and CFTR-mediated Cl(-) and HCO(3)(-) secretion. This may have implications in the future development of alternative treatment for constipation.

AIM:Colonic epithelium is known to secrete both Cl