Expression and clinical significance of HMGB1 in human liver cancer: Knockdown inhibits tumor growth and metastasis in vitro and in vivo

The high-mobility group box 1 (HMGB1) signaling pathway plays a crucialrole in tumorigenesis and progression of many malignant cancers. The present studyaimed to investigate the expression and clinical significance of HMGB1 in humanprimary liver cancer, and further explore the molecular mechanisms of HMGB1 intumor growth and metastasis. Forty cases of human liver cancer and normal livertissues were collected. The expression of HMGB1 was assessed using RT-PCR andwestern blot assays in biopsy samples. The HMGB1 pathway in vitro was blockedusing transfection of the recombinant small hairpin RNA adenovirus vector rAd5-HMGB1into the human liver cancer cell line SMMC-7721. The expression of HMGB1, phosphorylatedAKT (p-AKT), Ki-67 and matrix metallopeptidase-2 (MMP-2) was detected by Real-PCRand western blot assays. Cell proliferative activities and metastatic capabilitywere determined by MTT and Transwell assays. Cell cycle distribution and apoptosiswere detected by flow cytometry. A subcutaneous xenograft tumor model was established,validating the effects of rAd5-HMGB1 on tumor growth in vivo. As a consequence,HMGB1 was found to be highly expressed in liver cancer compared with normal tissues,and was positively associated with pathological grade and distant metastases ofliver cancer. Knockdown of HMGB1 downregulated the expression of p-AKT, Ki-67and MMP-2, inhibited the proliferative activities and metastatic potential ofSMMC-7721 cells, induced cell cycle arrest and apoptosis, and slowed the growthof xenograft tumors. Altogether, the expression of HMGB1 is closely correlatedwith pathological grade and distant metastases of liver cancer, and knockdownof HMGB1 inhibits liver cancer growth and metastasis, suggesting that HMGB1 maybe involved in liver cancer development and progression through AKT-mediated regulationof Ki-67 and MMP-2 expression, and represent a potential therapeutic target forthis aggressive malignancy.