title: Amiloride and guggulsterone suppression of esophageal cancer cell growth in vitro and in nude mouse xenografts.
abstract: Esophageal adenocarcinoma is increasing in the US and Western countries and frequent gastresophageal reflux or gastresophageal reflux disease carrying gastric acid and bile acid could contribute to esophageal adenocarcinogenesis. This study was designed to detect the expression of gastric acid-inducing gene Na + /H + exchanger-1 (NHE-1)ex vivoand then to explore targeting of NHE-1 expression or activity to control esophageal cancer cell viabilityin vitroand in nude mouse xenografts. The data showed that NHE-1 was highly expressed in esophageal adenocarcinoma tissues (66 of 101 cases [65.3%], but not in normal esophageal squamous cell epithelium (1 of 26 cases [3.8%]). Knockdown of NHE-1 expression using NHE-1 shRNA or inhibition of NHE-1 activity using the NHE-1 inhibitor amiloride suppressed viability and induced apoptosis in esophageal cancer cells. Molecularly, amiloride inhibited expression of cyclooxygenase-2 and matrix metallopeptidase-9 but not NHE-1 mRNA in esophageal cancer cells. A combination of amiloride and guggulsterone (a natural bile acid receptor inhibitor) showed more than additive effects in suppressing esophageal cancer cell growthin vitroand in nude mouse xenografts. This study suggests that inhibition of NHE-1 expression or activity or combination of amiloride and guggulsterone could be useful in control of esophageal adenocarcinoma.
authors.affiliation: Department of Clinical Cancer Prevention, Unit 1360, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX77030, USA.
authors.forename: Baoxiang
authors.initials: B
authors.lastname: Guan
authors.affiliation: Department of Clinical Cancer Prevention, Unit 1360, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX77030, USA.
authors.forename: Ashraful
authors.initials: A
authors.lastname: Hoque
authors.affiliation: Department of Clinical Cancer Prevention, Unit 1360, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX77030, USA ; Cancer Biology Program, The University of Texas Graduate School of Biomedical Sciences, Houston, TX 77225, USA.
authors.forename: Xiaochun
authors.initials: X
authors.lastname: Xu
keywords: NHE-1; amiloride; cell viability; esophageal cancer; guggulsterone