Dihydroartemisinin improves the efficiency of chemotherapeutics in lung carcinomas in vivo and inhibits murine Lewis lung carcinoma cell line growth in vitro

• Published in: Cancer chemotherapy and pharmacology 2010-05, Vol.66 (1), p.21-29
• Main Authors: Zhou, Hui-Jun, Zhang, Jia-Li, Li, Ao, Wang, Zeng, Lou, Xiao-E
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic agents; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - pharmacology; Antineoplastic Combined Chemotherapy Protocols - pharmacology; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Apoptosis - drug effects; Artemisinins - administration & dosage; Artemisinins - pharmacology; Biological and medical sciences; Cancer Research; Carcinoma, Lewis Lung - drug therapy; Cell Cycle - drug effects; Cell Proliferation - drug effects; Cell Survival - drug effects; Cisplatin - administration & dosage; Cisplatin - pharmacology; Cyclophosphamide - administration & dosage; Cyclophosphamide - pharmacology; Drug Screening Assays, Antitumor; Female; Humans; Medical sciences; Medicine; Medicine & Public Health; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Neoplasm Metastasis - drug therapy; Neoplasms - drug therapy; Neoplasms - metabolism; Oncology; Original Article; Pharmacology. Drug treatments; Pharmacology/Toxicology; Pneumology; Random Allocation; Tumor Burden - drug effects; Tumors of the respiratory system and mediastinum; Vascular Endothelial Growth Factor Receptor-2 - metabolism; Xenograft Model Antitumor Assays
• ISSN: 0344-5704; 1432-0843
• DOI: 10.1007/s00280-009-1129-z

Purpose Dihydroartemisinin (DHA), a semi-synthetic derivative of artemisinin, has exhibited the strongest antimalarial activity among the derivatives of artemisinin. There is growing evidence that DHA has some impact against tumors. Our purpose was to evaluate in vitro antitumoral properties of DHA in the murine Lewis lung carcinoma (LLC) cell line. At the same time, we observed the therapeutic effect of DHA combined with cyclophosphamide (CTX) in the LLC and combined with cisplatin (CDDP) in the human non-small cell lung cancer A549 xenotransplanted carcinoma in vivo. Methods Cytotoxicity was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method, apoptosis was measured by AO/EB double staining and flow cytometry. The expression of vascular endothelial growth factor (VEGF) receptor KDR/flk-1 was analyzed by western blotting and RT-PCR. In vivo activity of DHA combined with CTX or CDDP was assayed through tumor growth and metastasis. Results Dihydroartemisinin exhibited high anti-cancer activity in LLC cell line. DHA also induced apoptosis of LLC cells and influenced the expression of VEGF receptor KDR/flk-1. Furthermore, in both tumor xenografts, a greater degree of growth inhibition was achieved when DHA and chemotherapeutics were used in combination. The affection by DHA combined CTX on LLC tumor metastasis was significant. Conclusions Dihydroartemisinin is a potent compound against LLC cell line in vitro. In vivo, the combination strategy of DHA and chemotherapeutics holds promise for the treatment of relatively large and rapidly growing lung cancers.