title: Targeting HMGB1 inhibits bladder cancer cells bioactivity by lentivirus-mediated RNA interference.
abstract: High mobility group box 1(HMGB1) has been reported to be associate with tumor clinical stage and pathological grade in bladder cancer (BC). In this study, we investigated the underlying mechanism through lentivirus-mediated HMGB1 knockdown. HMGB1 was strongly inhibited in BC cells stably transfected with shRNA against HMGB1. MTT and colony formation assays demonstrated that the down-regulation of HMGB1 attenuated the growth of BC cells in vitro. The HMGB1 knockdown (KD) group displayed an increased proportion of cells in the G0/G1 phase and higher apoptosis rates of BC cells comparing with the control (CON) group. The transwell assay revealed that the KD group cells had much lower invasive activity. To assess the influence of HMGB1 inhibition on tumorigenicity in BC cells, shRNA-HMGB1 lentivirus were injected into the tumors of xenograft models and the results showed that the tumorigenesis in mice were significantly suppressed by shRNA-HMGB1 lentivirus. Furthermore, the expression level of VEGF-C in KD group was significantly decreased comparing with the CON group. The NF-κB inhibitor PDTC reduced the expression of VEGF-C, while HMGB1, as a NF-κB agonist, enhanced the VEGF-C expression. In conclusion, our results suggested that lentiviruses delivering shRNA against HMGB1 may be a promising tool for BC therapy.
authors.forename: W
authors.initials: W
authors.lastname: Wang
authors.forename: H
authors.initials: H
authors.lastname: Zhu
authors.forename: H
authors.initials: H
authors.lastname: Zhang
authors.forename: L
authors.initials: L
authors.lastname: Zhang
authors.forename: Q
authors.initials: Q
authors.lastname: Ding
authors.forename: H
authors.initials: H
authors.lastname: Jiang
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D024243:HMGB1 Protein / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology; D006801:Humans; D016086:Lentivirus / Q000235:genetics*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D034622:RNA Interference; D001749:Urinary Bladder Neoplasms / Q000473:pathology / Q000628:therapy*
chemical_list: D024243:HMGB1 Protein
keywords: HMGB1; RNA interference; bladder cancer; proliferation.