ABSTRACT
Objective To investigate the inhibitory effect of Withaferin A ( WFA) on the growth of orthotopic xenograft tumor of hepatocellular carcinoma in nude mice and the mechanism of its antitumoral effect. Methods For in vivo model, anti-tumor efficacy of Withaferin A was evaluated in nude mice mod-els of human liver cancer orthotopic xenograft. The nude mice were randomly divided into model group, Sunitinib group,and Withaferin A groups [6, 3 mg/(kg·d)]. All mice were given intraperitoneal injec-tion for 14 days. Tumor volume and tumor weight were observed. Antiangiogenic effects were assessed in vi-vo by the tumor inhibition rate and microvessel density. Quantitative polymerase chain reaction ( QPCR) as-say was used to detect the mRNA expression of vascular endothelial growth factor ( VEGF) , basic fibroblast growth factor (bFGF), angiopoietin-2 (Ang-2), vascular endothelial growth factor receptor 2 (VEGFR2) from tumor tissues. For in vitro experiments, the cell count kit 8 ( CCK8 ) assay was used to detect the effect of Withaferin A on HepG2 cells proliferation. QPCR assay and enzyme-linked immunosorbent assay ( ELISA) were used to detect the mRNA expression of VEGF. Results Compared to the model group, the high-dose Withaferin A group and the Sunitinib group had a significantly lower tumor weight (P<0. 05). The tumor inhibition rate was 42. 69％ in the high-dose Withaferin A group, 20. 22％ in the low-dose With-aferin A group, and 49. 43％ in the Sunitinib group. The growth of HepG2 cells was significantly inhibited by different concentrations of Withaferin A,and the 50％ concentration of inhibition ( IC50 ) of Withaferin A were (2. 64 ± 0. 18)μmol/L at 24 h. Withaferin A (6,3 μmol/L) could inhibit the protein and mRNA ex-pression of VEGF ( P<0. 05 ) . Conclusions Withaferin A significantly reduces the growth of orthotopic xenograft tumor of hepatocellular carcinoma in nude mice via antiangiogenic effect. Downregulation of the protein and mRNA expression of VEGF by WFA may be one mechanism of its anti-liver cancer effect.
ABSTRACT
Objective To review the efficacy and safety of brucea javanica oil in the adjuvant therapy of primary hepatocellular carcinoma (HCC).Methods China National Knowledge Infrastructure (CNKI),China Biology Medicine (CBM),VIP,Wanfang database,Pubmed,Web of Science,ScienceDirect,and Cochrane Library were searched from their inception to December 2015.Then contact with the field experts and correspondence authors for gray literature.Two reviewers independently searched the databases,performed data extraction,and appraised the publications.The Reviewer Manager 5.3 software was employed for data analysis.Results Fifteen clinical trials with 1 128 HCC patients were included.Meta-analysis confirmed that the brucea javanica oil group,compared to the control group,was more advantageous to reduce the incidence of postoperative fever,bone marrow suppression,and gastrointestinal reaction.In addition,it might reduce the level of alpha fetoprotein (AFP),enhance immunity,and improve clinical symptoms.However,more evidence would be needed to support these results.Conclusions Brucea javanica oil is considered to reduce toxicity and increase efficiency in the adjuvant therapy for the HCC,but more high quality,multi-center,large sample,randomized,double-blind clinical trials are also needed for supporting this view.
ABSTRACT
Objective To investigate the efficacy and safety of compound kushen injection (CKI)in the treatment for patients with advanced liver cancers.Methods Relevantly randomized controlled trials from China National Knowledge Infrastructure (CNKI),Chinese Science and Technology Journal Database (VIP),Wanfang Data,and Pubmed were searched until November,2014.Randomized controlled trials (RCTs) of supportive care compared with combined therapy of CKI in the treatment for patients with advanced liver cancers were included.The methodological quality of RCTs was assessed independently with bias risk according to the Cochrane collaboration.All data were analyzed with the Review Manager 5.3.Results Eight RCTs involving 472 patients were included.The meta-analysis results suggested that the shortterm efficacy of the treatment group be higher (P =0.008) and that the pain relief be a significant benefit in the treatment group (P ＜0.01).Adverse reactions were not observed.Conclusions CKI is an effective and safe adjuvant drug for advanced liver cancers.