Background and purpose: In addition to its central role in maintaining normal biorhythms

the abnormal expression of rhythm factor BMAL1 may also be involved in the evolution of various tumors. However

the mechanism of action has not been fully elucidated. This study aimed to investigate the effect of BMAL1 on the proliferation of gastric cancer cells and downstream signaling pathways. Methods: si-BMAL1 or negative control (NC) was transfected into the MGC-803 cells

and then Western blot was used to detect the transfection efficiency. The cell viability and proliferation were examined by MTT assay and plate colony formation assay

respectively. The protein level of cyclin D1 and the expressions of SHH signaling pathway-related proteins SHH

SMO and GLI1 in the MGC-803 cells were determined by Western blot. After cyclopamine

a SHH signaling pathway inhibitor was used to treat the gastric cancer MGC-803 cells with BMAL1 knockdown

Western blot was used to detect the protein levels of cyclin D1

SHH

SMO and GLI1. Plate colony formation assay was used to measure the viability of the cells. Results: Compared with NC group，the expression of BMAL1 in si-BMAL1 group was significantly down-regulated，and the cell proliferation was increased. The protein levels of cyclin D1

SHH

SMO and GLI1 in the cells were increased (P0.05). After treatment with SHH inhibitor cyclopamine

the protein levels of SHH

SMO and GLI1 were lower in si-BMAL1+cyclopamine group than in NC group

while cyclin D1 did not change. SHH signaling pathway inhibitor reversed BMAL1 knockdown-induced increase in viability of MGC-803 cells. Conclusion: BMAL1 inhibits the growth of gastric cancer cells through SHH signaling pathway.