WTSA: Inhibition of Group IIa Secretory Phospholipase A<sub>2</sub> Suppresses Proliferation in Human Esophageal Adenocarcinoma Cells

WTSA: Western Thoracic Surgical Association

Search


Home

Annual Meeting

Members
	Member Directory
	Join WTSA
	Members Only

Council

Committees

Journal

Newsletters

Awards

Links

Inhibition of Group IIa Secretory Phospholipase A₂ Suppresses Proliferation in Human Esophageal Adenocarcinoma Cells

David C Mauchley, Xianzhong Meng, *David A Fullerton, *Michael J Weyant
University of Colorado, Aurora, CO

BACKGROUND: The incidence of esophageal adenocarcinoma (EAC) is rapidly rising in the western world. This phenomenon is thought to be directly related to gastroesophageal reflux disease (GERD). We have previously demonstrated in vivo that the enzyme group IIa secretory phospholipase A₂ (sPLA₂) is necessary for the development of early histologic changes in esophageal mucosa in response to surgically-induced GERD. This enzyme has been found to be overexpressed in esophageal adenocarcinoma but its role is not known. We sought to determine the influence of group IIa sPLA₂ on EAC cell proliferation.
METHODS: FLO-1 cells derived from human EAC were subcultured at a density of 2 x 10⁴in 96-well plates in Dulbecco’s modified Eagle’s medium (DMEM) supplemented with 10% fetal calf serum (FCS) and 1% penicillin/streptomycin, and grown for 72 hours at 37°C. Cells were then serum starved for 24 hours to induce cell cycle arrest. After this period, cells were stimulated with acidic medium (pH=4.5) for 90 minutes in the presence of 0.1-10 μM concentrations of the sPLA₂ inhibitor (5-(4-benzyloxyphenyl)-4S-(7-phenylheptanoylamino)-pentanoic acid or vehicle (DMSO). Cells were then allowed to proliferate for six hours in 10% FCS containing medium and assessed for cell number and proliferation with 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) and bromodeoxyuridine (BrdU) incorporation assays respectively. All assays were performed in triplicate. Statistical analysis was determined using student’s t-test.
RESULTS: Treatment with the sPLA₂ inhibitor resulted in a significant reduction of growth and proliferation of EAC cells compared to controls (Figs. 1 & 2).
CONCLUSIONS: Group IIa sPLA₂appears to play a significant role in the growth and proliferation of human EAC cells. This novel finding implies that sPLA₂ inhibition should be studied further regarding its role as a potential chemopreventative and therapeutic agent in EAC.

Back to 2009 Annual Meeting
Back to Main Program

Home | About WTSA | Contact Us

www.westernthoracic.org