Abstract: Objective To investigate the effect of proteasome inhibitor bortezomib on the growth of esophageal squamous cell carcinoma（ESCC）. Methods Based on whole genome sequencing data，DGIdb database was used to screen esophageal squamous cell carcinoma-related druggable genes，and KEGG signal pathway enrichment analysis was performed using DAVID software. The effect of bortezomib on the growth of 5 ESCC cells including KYSE30，KYSE180，KYSE150，TE1and KYSE510 were measured by MTT，and DMSO-treated cells were used as the corresponding control group. Nude mice were injected intraperitoneally with saline （control group） and bortezomib （bortezomib group） after tumor formation in vitro. The effects of bortezomib on the volume and weight of xenografts in nude mice were observed.Immunohisto-chemistry was performed to determine the expression of Ki-67 protein in xenograft tumor tissues treated with bortezomib. Results A total of 307 druggable genes were identified from genomics sequencing data of 469 ESCC cases in the DGIdb database，and the significantly mutated druggable genes with mutation frequencies>2.5% included PIK3CA，NOTCH1，CDKN2A，ERBB4，etc.The enriched signaling pathways of all druggable genes included RTK-RAS，PI3K/AKT/mTOR，NOTCH，ERBB signaling pathway，cell cycle and proteasome pathway，etc. MTT results showed that the proliferation of 5 ESCC cell lines treated with bortezomib were significantly inhibited compared with control group（P<0.05）. Compared with the control group，the tumor volume of the bortezomib group was significantly decreased［（1 909.18±533.40） mm³ vs （1 065.83±283.94） mm³，P<0.01］，and the tumor weight of the bortezomib group was also significantly decreased ［（1.60±0.36） g  vs （0.98±0.30） g，P<0.01］. Immunohistochemistry showed that the expression of Ki-67 in the bortezomib group was significantly decreased compared with the control group （43.83±3.22  vs 86.32±4.51，P<0.01）. Conclusion Bortezomib can inhibit the cell growth of ESCC in vitro and in vivo.

Key words: Esophageal squamous cell carcinoma, Targeted therapy；Signaling pathway；Proteasome；Bortezomib