title: Evaluation of the Antitumor Efficacy of RNAi-Mediated Inhibition of CDC20 and Heparanase in an Orthotopic Liver Tumor Model.
abstract: Over 90% of patients with hepatocellular carcinoma (HCC) are diagnosed at an advanced stage. This study investigated the antitumor efficacy of the inhibition of cell division cycle protein 20 (CDC20) and heparanase (HPSE) expression in Hepa1-6 mouse hepatoma cells. Cell viability was measured by the MTT assay. Cell cycle was analyzed by cytometry. The invasion assay was performed using the Transwell chamber. The orthotopic liver tumor model was established by inoculating the livers of immunocompetent Kunming mice with Hepa1-6 cells. The MTT assay showed that 50 and 100 nM CDC20 siRNA-1 and HPSE siRNA-2 significantly reduced Hepa1-6 cell viability with the combination of CDC20 and HPSE siRNA being the most effective. Silencing of CDC20 or both CDC20 and HPSE expression significantly induced G2/M phase cell cycle arrest in Hepa1-6 HCC cells. Silencing HPSE expression significantly inhibited the invasion ability of Hepa1-6 cells with the combination of CDC20 and HPSE silencing being more effective than HPSE alone. Silencing CDC20 and HPSE expression significantly inhibited HCC tumor growth in the orthotopic liver tumor model, but the combination was most effective. Silencing CDC20 and HPSE expression activated cell apoptosis and autophagy. In conclusion, targeting inhibition of both CDC20 and HPSE expression is an ideal strategy for HCC therapy.
authors.affiliation: 1 Hepatobiliary Enteric Surgery Research Center, Xiangya Hospital, Central South University , Changsha, People's Republic of China .
authors.forename: Meizhou
authors.initials: M
authors.lastname: Liu
authors.affiliation: 1 Hepatobiliary Enteric Surgery Research Center, Xiangya Hospital, Central South University , Changsha, People's Republic of China .
authors.forename: Yangde
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: 2 Second People's Hospital of Shenzhen , Shenzhen, People's Republic of China .
authors.forename: Yunjun
authors.initials: Y
authors.lastname: Liao
authors.affiliation: 2 Second People's Hospital of Shenzhen , Shenzhen, People's Republic of China .
authors.forename: Yixing
authors.initials: Y
authors.lastname: Chen
authors.affiliation: 1 Hepatobiliary Enteric Surgery Research Center, Xiangya Hospital, Central South University , Changsha, People's Republic of China .
authors.forename: Yifeng
authors.initials: Y
authors.lastname: Pan
authors.affiliation: 3 Department of General Surgery, Shandong Provincial Qianfoshan Hospital, Shandong University , Qianfoshan, People's Republic of China .
authors.forename: Hu
authors.initials: H
authors.lastname: Tian
authors.affiliation: 2 Second People's Hospital of Shenzhen , Shenzhen, People's Republic of China .
authors.forename: Yongqiang
authors.initials: Y
authors.lastname: Zhan
authors.affiliation: 1 Hepatobiliary Enteric Surgery Research Center, Xiangya Hospital, Central South University , Changsha, People's Republic of China .
authors.forename: Dongjing
authors.initials: D
authors.lastname: Liu
mesh_terms: D000818:Animals; D064199:Cdc20 Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004195:Disease Models, Animal; D005966:Glucuronidase / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D034622:RNA Interference / Q000502:physiology*; D014162:Transfection; D000099175:Heparanase
chemical_list: D064199:Cdc20 Proteins; D005966:Glucuronidase; D000099175:Heparanase; C577488:CDC20 protein, human
keywords: CDC20; RNA interference; animal model; heparanase; liver cancer