Inhibitive Effect of Artemether on Tumor Growth and Angiogenesis in the Rat C6 Orthotopic Brain Gliomas Model

Abstract

To explore the inhibitive effect of artemether on glioma growth and angiogenesis in brain tumor bearing SD rat. MTT assay was used to evaluate the inhibitory effect of artemether treatment on C6 glioma cells. Forty SD rats which were subcutaneous planted with SD rat C6 glioma cell to establish SD rat orthotopic glioma model were divided resourcefully into 5 groups. each group was 8 rats. Length-path (a mm) and short-path (b mm) of tumor each rat was measured. Tumor volume was calculated using the following formula: V (mm³) = a²b_/6. Microvessel density (MVD) in different therapy groups was significantly lower than that in normal saline control group and brain glioma volume in different therapy groups was significantly smaller than that in normal saline control group. There were remarkably inhibitory effects of artmeter on brain glioma growth and angiogenesis in SD rats and the mechanism that artemether inhibited brain glioma growth might be penetrating the blood-brain barrier and inhibiting angiogenesis.

Keywords

artemether SD rat C6 glioma cell line brain glioma animal model angiogenesis

References

Prados MD , Levin V. Biology and treatment of malignant glioma. Semin Oncol. 2000;27(3 suppl 6):1-10.

Folkman J. Role of angiogenesis in tumor growth and metastasis. Semin Oncol. 2002;29(6):15-18.

Bogler O. , Mikkelsen T. Angiogenesis in glioma: molecular mechanisms and roadblocks to translation . Cancer. 2003;9: 205-213.

Kaur B. , Tan C. , Brat DJ , et al. Genetic and hypoxic regulation of angiogenesis in gliomas. J Neurooncol. 2004;70:229-243.

Parthymou A. , Kardamakis D. , Pavlopoulos I. , Papadimitriou E. Irradiated C6 glioma cells induce angiogenesis in vivo and activate endothelial cells in vitro. Int J Cancer . 2004;110:807-814.

Lai H. , Singh NP Oral artemisinin prevents and delays the development of 7, 12-dimethylbenz [a] anthracene (DMBA)-induced breast cancer in the rat. Cancer Lett. 2006;231: 43-48.

Singh NP , Lai H. Synergistic cytotoxicity of artemisinin and sodium butyrate on human cancer cells. Anticancer Res. 2005;25(6B):4325-4331.

Singh NP , Lai H. Selective toxicity of dehydroartemisinin and holotransferrin on human breast cancer cells. Life Sci. 2001; 70:49-56.

Shterman N. , Kupfer B. , Moroz C. Comparison of transferring receptors, iron content and isoferritin profile in normal and malignant human breast cell lines. Pathobiology . 1991;59: 19-25.

10.

Efferth A. , Dunstan H. , Sauerbrey A. , et al. The anti-malarial artesunate is also active against cancer. Int J Oncol. 2001;18: 767-773.

11.

Kim SJ , Kim MS , Lee JW , et al. Dihydroartemisinin enhances radiosensitivity of human glioma cells in vitro. J Cancer Res Clin Oncol. 2006 ;132:129-135.

12.

Zhi-ping W. , Cheng-wei G. , Xi-cai W. , et al. An experimental study on inhibitory effect of artemether on colorectal cancer angiogenesis in BALB/c mice. China Cancer. 2007;12.

13.

Kuo HC , Kuo WH , Lee YJ , Lin WL , Chou FP , Tseng TH Inhibitory effect of caffeic acid phenethyl ester on the growth of C6 glioma cells in vitro and in vivo. Cancer Lett. 2006 ;234: 199-208.

14.

Lee JI , Itasaka S. , Kim JT , et al. Antiangiogenic agent, thalidomide increases the antitumor effect of single high dose irradiation (gamma knife radiosurgery) in the rat orthotopic glioma model. Oncol Rep. 2006;15:1163-1168.

15.

Nam DH , Park K. , Park C. , et al. Intracranial inhibition of glioma cell growth by cyclooxygenase-2 inhibitor celecoxib. Oncol Rep. 2004;11:263-268.

16.

Folkman J. Tumor angiogenesis: therapeutic implications. N Engl J Med . 1971;285:1182-1186.

17.

Folkman J. Clinical applications of research on angiogenesis. N Engl J Med. 1995;333:1757-1763.

18.

Bergers G. , Benjamin LE Tumorigenesis and the angiogenic switch. Nat Rev Cancer. 2003;3:401-410.

19.

Kerbel RS Tumor angiogenesis. N Engl J Med. 2008;358: 2039-2049.

20.

Jain RK , di Tomaso E. , Duda DG , et al. Angiogenesis in brain tumours. Nat Rev Neurosci . 2007;8:610-622.

21.

Davis TM , Binh TQ , Ilett KF , et al. Penetration of dihydroartemisinin into cerebrospinal fluid after administration of intravenous artesunate in severe falciparum malaria. Antimicrob Agents Chemother. 2003;47:368-370.

22.

Klayman D. Qinghaosu (artemisinin): antimalarial drug from China. Science . 1985;228:1049-1055.

23.

Zhou HJ , Wang WQ , Wu GD , et al. Artesunate inhibits angiogenesis and downregulates vascular endothelial growth factor expression in chronic myeloid leukemia K562 cells . Vascul Pharmacol. 2007;47(2-3):131-138.

24.

Lai H. , Tomikazu S. , Singh NP Targeted treatment of cancer with artemisinin and artemisinin tagged iron-carrying compounds. Expert Opin. 2005;9:995-1007.

25.

Singh NP , Lai H. Synergistic cytotoxicity of artemisinin and sodium butyrate on human cancer cells. Anticancer Res. 2005;25(6B):4325-4331.