title: Mechanism of QHF-cisplatin against hepatocellular carcinoma in a mouse model.
abstract: OBJECTIVE
  To study the effects of QHF-cisplatin on H22 hepatocellular carcinoma (HCC) and their mechanisms of action.
  
  
  METHODS
  Sixty BALB/c mice were randomly divided into a model group (n = 48) and a normal control group (n = 12). An HCC xenograft tumor was created by injecting H22 cells directly into the liver parenchyma of the mice. The 48 BALB/c mice in the model group were randomly divided into four groups: QHF, DDP (cisplatin), QHF plus DDP, and model control. The inhibitory effects of these drugs on tumor growth were evaluated by calculating the rate of tumor growth inhibition. The mice were examined by observing their general condition, body weight and survival time. Changes in tumor tissue were observed under an optical microscope. Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and α-fetoprotein (AFP) levels in serum were measured. Hepatocyte growth factor (HGF), c-mesenchymal-epithelial transition (c-Met) factor, phosphorylated (p)-c-Met, p38, p-p38, extracellular signal-regulated kinase (ERK), p-ERK and vascular endothelial growth factor (VEGF) levels were evaluated in tumor and liver tissues using western blotting.
  
  
  RESULTS
  Compared with the DDP group, a lower incidence of toxic reactions and a higher survival time were observed in the QHF plus DDP group. Tumor weight was significantly lower in the QHF, DDP and QHF plus DDP groups than in the model control group (0.24 ± 0.07, 0.18 ± 0.03 and 0.14 ± 0.01 g vs 0.38 ± 0.05 g, respectively), and the differences were statistically significant (P < 0.01). The rate of tumor growth inhibition in the QHF, DDP and QHF plus DDP groups was 38.7%, 52.6% and 63.5%, respectively. AST, ALT and AFP levels in serum were significantly lower in the QHF, DDP and QHF plus DDP groups compared to the model control group (P < 0.05). Similarly, HGF, p-c-Met, p-p38, p-ERK and VEGF levels in tumor tissue were significantly lower in the QHF, DDP and QHF plus DDP groups (P < 0.05).
  
  
  CONCLUSIONS
  QHF and DDP have an antiangiogenic effect on H22 HCC in mice. QHF inhibits tumor growth via blocking the HGF/c-Met signaling pathway, inhibiting p38, ERK and VEGF signaling.
authors.affiliation: Tao Chen, Wei Hu, the Third Level of TCM Pharmacology Research Laboratory affiliated to China TCM Administration, Medical Science College of China Three Gorges University, Yichang 443002, Hubei Province, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Chen
authors.affiliation: Tao Chen, Wei Hu, the Third Level of TCM Pharmacology Research Laboratory affiliated to China TCM Administration, Medical Science College of China Three Gorges University, Yichang 443002, Hubei Province, China.
authors.forename: Shen-Jun
authors.initials: SJ
authors.lastname: Yuan
authors.affiliation: Tao Chen, Wei Hu, the Third Level of TCM Pharmacology Research Laboratory affiliated to China TCM Administration, Medical Science College of China Three Gorges University, Yichang 443002, Hubei Province, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Tao Chen, Wei Hu, the Third Level of TCM Pharmacology Research Laboratory affiliated to China TCM Administration, Medical Science College of China Three Gorges University, Yichang 443002, Hubei Province, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Hu
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D014408:Biomarkers, Tumor / Q000097:blood; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D005260:Female; D008114:Liver Neoplasms, Experimental / Q000097:blood / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008807:Mice, Inbred BALB C; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D020533:Angiogenesis Inhibitors; D014408:Biomarkers, Tumor; D004365:Drugs, Chinese Herbal; D002945:Cisplatin
keywords: Cisplatin; H22 cells; Hepatocellular carcinoma; Hepatocyte growth factor; QHF formula; c-Met