title: Effect of halofuginone on the inhibition of proliferation and invasion of hepatocellular carcinoma HepG2 cell line.
abstract: Primary liver cancer is a common cancer and the mortality of liver cancer ranks the second of all malignancy-related deaths in China. The most common primary liver cancer is hepatocellular carcinoma, accounting for approximately 90% of the total. Because liver is the largest parenchymatous organ in the body undertaking all kinds of important metabolic functions, liver cancer inevitably causes greater harms and its treatment is extremely difficult. Currently, there are still no effective drugs for the treatment of patients with advanced inoperable liver cancer. We observed the strong inhibitory activity of halofuginone on HepG2 cell growth and the cell cycle and apoptosis assays showed that halofuginone arrested the cell cycle and inhibited the induction. And we found that halofuginone inhibits tumor cell cycle possibly by up-regulating p15 and p21 of expression. Then, we found that the proportion of cleaved PARP, caspase-3, 8 and 9 in HepG2 cells increased after halofuginone treatment. And the results showed that halofuginone down-regulated Mcl-1 and c-IAP1 expression. Finally, our results showed halofuginone regulated the activities of JNK and MEK/ERK signaling pathways in hepatocellular carcinoma cells. In summary, this study shows that halofuginone can inhibit the in vitro growth, arrest the cell cycle and induce the apoptosis of HepG2 cells. Its mechanisms of action may be related to the regulation of associated protein expression, up-regulation of JNK, and inhibition of MEK/ERK signaling pathway.
authors.affiliation: Department of Pharmacy, China-Japan Union Hospital, Jilin University Changchun 130033 China.
authors.forename: Sibo
authors.initials: S
authors.lastname: Huo
authors.affiliation: Department of Pharmacy, China-Japan Union Hospital, Jilin University Changchun 130033 China.
authors.forename: Huiqiu
authors.initials: H
authors.lastname: Yu
authors.affiliation: Department of Pharmacy, China-Japan Union Hospital, Jilin University Changchun 130033 China.
authors.forename: Chusheng
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Pharmacy, China-Japan Union Hospital, Jilin University Changchun 130033 China.
authors.forename: Jiayu
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Colorectal and Anal Surgery, China-Japan Union Hospital, Jilin University Changchun 130033, China.
authors.forename: Tongjun
authors.initials: T
authors.lastname: Liu
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D018797:Cell Cycle Proteins / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009361:Neoplasm Invasiveness; D010880:Piperidines / Q000494:pharmacology*; D052999:Quinazolinones / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; D018797:Cell Cycle Proteins; D010880:Piperidines; D052999:Quinazolinones; C010176:halofuginone
keywords: Halofuginone; hepatocellular carcinoma; invasion; proliferation