title: DHA regulates angiogenesis and improves the efficiency of CDDP for the treatment of lung carcinoma.
abstract: Dihydroartemisinin (DHA), a semisynthetic derivative of artemisinin, has been shown to exhibit anti-angiogenic and anti-tumor effects apart from its antimalarial activity. In this study, we demonstrate that the combined treatment of cisplatin (CDDP) and DHA exerts a strong, synergistic anti-proliferative effect in human lung carcinoma cells, including A549 and A549/DDP cells, with an average combination index below 0.7. Moreover, the in vivo anti-tumor efficacy of CDDP treatment was increased by DHA. The enhanced anti-cancer activities were also accompanied by reduced tumor microvessel density, increased CDDP concentration within A549 and A549/DDP xenograft BALB/c athymic mice models and suppressed expression of the vascularization-related proteins HIF-1α and VEGF both in vivo and in vitro. Furthermore, the level of apoptosis in the tumor cells increased with the combined treatment of DHA and CDDP. Taken together, our results indicate that a combination of DHA and CDDP treatments synergistically affects tumor angiogenesis, and these results provide a clear rationale for the investigation of these drugs in future clinical trials.
authors: Institute of Pharmacology and Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, People's Republic of China.
authors: Jia-Li
authors: JL
authors: Zhang
authors: Zeng
authors: Z
authors: Wang
authors: Wei
authors: W
authors: Hu
authors: Sang-Sang
authors: SS
authors: Chen
authors: Xiao-E
authors: XE
authors: Lou
authors: Hui-Jun
authors: HJ
authors: Zhou
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000378:metabolism / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D037621:Artemisinins / Q000008:administration & dosage; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D004357:Drug Synergism; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D008175:Lung Neoplasms / Q000098:blood supply* / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D055806:Microvessels / Q000187:drug effects / Q000473:pathology; D009389:Neovascularization, Pathologic; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D020533:Angiogenesis Inhibitors; D037621:Artemisinins; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C039060:artenimol; D002945:Cisplatin