title: Combination of onconase and dihydroartemisinin synergistically suppresses growth and angiogenesis of non-small-cell lung carcinoma and malignant mesothelioma.
abstract: Onconase (Onc) is a cytotoxic ribonuclease derived from leopard frog oocytes or early embryos, and has been applied to the treatment of malignant mesothelioma in clinics. Onc also exhibits effective growth suppression of human non-small-cell lung cancer (NSCLC). Artemisinin (Art) and its derivatives are novel antimalarial drugs that exhibit antitumor and antivirus activities. In this study, we investigated the antitumor effects of combinations of Onc and an Art derivative, dihydroartemisinin (DHA), both in vitro and in vivo Isobologram analyses showed synergistic effects on the proliferation of NSCLC cells under the treatment with Onc and DHA. In vivo experiments also showed that the antitumor effect of Onc was markedly enhanced by DHA in mouse xenograft models. No obvious adverse effect was observed after the treatment. The density of microvasculature in the tumor tissues treated with Onc/DHA combination was lower than those treated with Onc or DHA alone. The above results are consistent with the results of the matrigel plug test for angiogenesis suppression using the Onc/DHA combination. These results imply that the anti-angiogenesis effects may make important contributions to the in vivo antitumor effects of the Onc/DHA combination treatment. The Onc/DHA combination therapy may have the potential to become a novel regimen for NSCLC and mesothelioma.
authors: School of Life Science and Technology, Tongji University, Shanghai 200092, China Shanghai Research Center for Model Organisms, Pudong New Area, Shanghai 201203, China.
authors: Ruling
authors: R
authors: Shen
authors: Shanghai Research Center for Model Organisms, Pudong New Area, Shanghai 201203, China.
authors: Jun
authors: J
authors: Li
authors: Shanghai Research Center for Model Organisms, Pudong New Area, Shanghai 201203, China.
authors: Danrong
authors: D
authors: Ye
authors: Shanghai Research Center for Model Organisms, Pudong New Area, Shanghai 201203, China 13764778109@163.com jfei@tongji.edu.cn.
authors: Qingcheng
authors: Q
authors: Wang
authors: School of Life Science and Technology, Tongji University, Shanghai 200092, China Shanghai Research Center for Model Organisms, Pudong New Area, Shanghai 201203, China 13764778109@163.com jfei@tongji.edu.cn.
authors: Jian
authors: J
authors: Fei
mesh_terms: D000072283:A549 Cells; D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D037621:Artemisinins / Q000008:administration & dosage / Q000494:pharmacology; D002289:Carcinoma, Non-Small-Cell Lung / Q000098:blood supply / Q000188:drug therapy* / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004357:Drug Synergism; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D008654:Mesothelioma / Q000098:blood supply / Q000188:drug therapy* / Q000378:metabolism; D000086002:Mesothelioma, Malignant; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000517:prevention & control*; D012260:Ribonucleases / Q000008:administration & dosage / Q000494:pharmacology; D047368:Tumor Burden / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D000962:Antimalarials; D000970:Antineoplastic Agents; D037621:Artemisinins; D042461:Vascular Endothelial Growth Factor A; C039060:artenimol; D012260:Ribonucleases; C058703:ranpirnase
keywords: anti-angiogenesis effect; dihydroartemisinin; mesothelioma; non–small-cell lung cancer; onconase; synergistic effect