Results: Our results shown that melatonin at concentration of 200 and 100 micro molar at 48 hr, has significant anti-proliferative effect compared with control and at 100 and 50 micro molar has significant apoptotic effect. Conclusion: According to the results we can conclude that melatonin in high concentrations can have antiproliferative and apoptotic effect against gastric adenocarcinoma cell line and as this drug is with

low adverse effect we can suggest it as co-supplement for gastric cancer chemotherapy but much more in-vivo and clinical trials are needed. Key Word(s): 1. melatonin; Dorsomorphin in vivo 2. proliferative; 3. apoptosis; 4. gastric cancer; Presenting Author: ZHEN HE Additional Authors: SHUTIAN ZHANG Corresponding Author: ZHEN HE Affiliations: Beijing Friendship Hospital Affiliated to the Capital Medical University Objective: Our previous study found that the proliferation of ESCC cells induced by EGFR activation can be inhibited by β-adrenergic receptor blockers. We hypothesized that EGFR activation promote tumor growth by the β2-adrenergic receptor / COX-2 pathway. This study aimed to explore whether EGFR activation can promote the COX-2 expression and

tumor growth by β2-adrenergic receptor Adriamycin mouse (ADRB2) pathways in ESCC cells and nude mouse model, and investigate the relationship of EGFR and COX-2 expression in human ESCC specimens. Methods: Human ESCC cell line KYSE30 was treated with EGF, EGFR inhibitor (AG1478), β2-selective antagonist (ICI 118551) and cyclooxygenase-2 inhibitor (nimesulide). Cell

survival was tested with MTT assay. The expression of COX-2 was detected by western blot and real-time reverse transcription PCR. Human ESCC xenograft in nude mice was administered with EGF combining or not combining EGFR inhibitor, β2-selective antagonist and cyclooxygenase-2 inhibitor. Tumor growth was observed and COX-2 expression was detected by western blot and real-time reverse transcription PCR. Western blotting was used to test ESCC and adjacent noncancerous tissue, the tissue samples were divided into two groups according to the level of EGFR protein expression, then COX-2 expression was detected. selleck chemicals llc Immunohistochemistry was applied to of detect the the expression of of EGFR and COX-2 in ESCC tissue, then the relationship between the EGFR and COX-2 expression was evaluated. Results:  (1)  EGFR, β2-adrenergic receptor and COX-2 was expressed in KYSE 30 cells. EGF stimulated KYSE30 cell proliferation in a dose-dependent manner. AG1478 (EGFR inhibitor), ICI 118551, (β2-selective antagonist) and nimesulide (highly selective cyclooxygenase-2 inhibitor) attenuated cell proliferation induced by EGF. AG1478 and ICI 118,551 also abrogated EGF-induced upregulation of COX-2 expression in the mRNA and protein level. Conclusion: These data provided the first evidence that EGFR activation resulted in enhanced expression of COX-2 and tumor growth through activation of β2-adrenergic receptor in ESCC.