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

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Abstract

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.

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Acknowledgments

This work was supported in part by a grant from the Zhejiang Provincial Science and Technology Program (No. 2008C23067) and by funds for scientific research from Health Bureau of Zhejiang Province (No. 2008W10923), China.

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Authors and Affiliations

  1. Institute of Pharmacology and Toxicology, College of Pharmaceutical Sciences, Zhejiang University, 388 Yuhang’tang Road, Hangzhou, Zhejiang, 310058, People’s Republic of China

    Hui-Jun Zhou, Jia-Li Zhang, Ao Li, Zeng Wang & Xiao-E Lou

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  1. Hui-Jun Zhou
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  2. Jia-Li Zhang
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Correspondence to Hui-Jun Zhou.

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Zhou, HJ., Zhang, JL., Li, A. et al. Dihydroartemisinin improves the efficiency of chemotherapeutics in lung carcinomas in vivo and inhibits murine Lewis lung carcinoma cell line growth in vitro. Cancer Chemother Pharmacol 66, 21–29 (2010). https://doi.org/10.1007/s00280-009-1129-z

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  • DOI: https://doi.org/10.1007/s00280-009-1129-z

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