Reversal of multidrug resistance by the anti‑malaria drug artesunate in the esophageal cancer Eca109/ABCG2 cell line

Liu,Liang; Zuo,Lian  Fu; Guo,Jian   Wen

doi:10.3892/ol.2013.1545

Reversal of multidrug resistance by the anti‑malaria drug artesunate in the esophageal cancer Eca109/ABCG2 cell line

Authors:
- Liang Liu
- Lian Fu Zuo
- Jian Wen Guo
View Affiliations

Affiliations: Department of Flow Cytometry Analysis, Tumor Institute, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China
Published online on: August 23, 2013 https://doi.org/10.3892/ol.2013.1545
Pages: 1475-1481

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The overexpression of ATP‑binding cassette (ABC) transporters confers multidrug resistance (MDR) to tumor cells. ABCG2 is a member of the ABC superfamily. The present study aimed to investigate the correlation between ABCG2 expression and the MDR of esophageal cancer and to estimate the therapeutic benefit of downregulating ABCG2 expression and reversing chemoresistance in esophageal cells using artesunate (Art). The Eca109/ABCG2 cell line was established by transfecting the ABCG2 gene into Eca109 cells. The Eca109/ABCG2 esophageal cancer cells with ABCG2 gene overexpression were resistant to adriamycin (ADM), daunorubicin (DNR) and mitoxantrone (MIT), which indicated that ABCG2 may be associated with drug resistance in esophageal cancer. Art is a noteworthy antimalarial agent, particularly in severe and drug‑resistant cancer cases, as Art is able to reverse drug resistance. In the present study, Art also exerted profound anticancer activity. The mechanism for the reversal of multidrug resistance by Art in esophageal carcinoma was analyzed using cellular experiments, but still remains largely unknown.

View Figures

View References

1	Gamliel Z: Incidence, epidemiology, and etiology of esophageal cancer. Chest Surg Clin N Am. 10:441–450. 2000.PubMed/NCBI
2	Mehta NG and Mehta M: Overcoming multidrug-resistance in cancer: statins offer a logical candidate. Med Hypotheses. 74:237–239. 2010. View Article : Google Scholar : PubMed/NCBI
3	Katayama R, Koike S, Sato S, Sugimoto Y, Tsuruo T and Fujita N: Dofequidar fumarate sensitizes cancer stem-like side population cells to chemotherapeutic drugs by inhibiting ABCG2/BCRP-mediated drug export. Cancer Sci. 100:2060–2068. 2009. View Article : Google Scholar : PubMed/NCBI
4	Gillet JP and Gottesman MM: Mechanisms of multidrug resistance in cancer. Methods Mol Biol. 596:47–76. 2010. View Article : Google Scholar : PubMed/NCBI
5	Fojo T and Coley HM: The role of efflux pumps in drug-resistant metastatic breast cancer: new insights and treatment strategies. Clin Breast Cancer. 7:749–756. 2007. View Article : Google Scholar : PubMed/NCBI
6	Gottesman MM, Fojo T and Bates SE: Multidrug resistance in cancer: role of ATP-dependent transporters. Nat Rev Cancer. 2:48–58. 2002. View Article : Google Scholar : PubMed/NCBI
7	Gottesman MM, Ambudkar SV and Xia D: Structure of a multidrug transporter. Nat Biotechnol. 27:546–547. 2009. View Article : Google Scholar : PubMed/NCBI
8	Mao Q and Unadkat JD: Role of the breast cancer resistance protein (ABCG2) in drug transport. AAPS J. 7:E118–E133. 2005. View Article : Google Scholar : PubMed/NCBI
9	Liu HG, Pan YF, You J, Wang OC, Huang KT and Zhang XH: Expression of ABCG2 and its significance in colorectal cancer. Asian Pac J Cancer Prev. 11:845–848. 2010.PubMed/NCBI
10	Shanks GD: For severe malaria, artesunate is the answer. Lancet. 376:1621–1622. 2010. View Article : Google Scholar : PubMed/NCBI
11	Zoller T, Junghanss T, Kapaun A, Gjorup I, Richter J, Hugo-Persson M, Mørch K, Foroutan B, Suttorp N, Yürek S and Flick H: Intravenous artesunate for severe malaria in travelers, Europe. Emerg Infect Dis. 17:771–777. 2011. View Article : Google Scholar : PubMed/NCBI
12	Bello SO: Pre-referral artesunate in severe malaria. Lancet. 373:1762–1763. 2009. View Article : Google Scholar : PubMed/NCBI
13	Zeng Y, Ni X, Meng WT, Wen Q and Jia YQ: Inhibitive effect of artesunate on human lymphoblastic leukemia/lymphoma cells. Sichuan Da Xue Xue Bao Yi Xue Ban. 40:1038–1043. 2009.(In Chinese).
14	Steinbrück L, Pereira G and Efferth T: Effects of artesunate on cytokinesis and G₂/M cell cycle progression of tumour cells and budding yeast. Cancer Genomics Proteomics. 7:337–346. 2010.PubMed/NCBI
15	Hamacher-Brady A, Stein HA, Turschner S, Toegel I, Mora R, Jennewein N, Efferth T, Eils R and Brady NR: Artesunate activates mitochondrial apoptosis in breast cancer cells via iron-catalyzed lysosomal reactive oxygen species production. J Biol Chem. 286:6587–6601. 2011. View Article : Google Scholar
16	Michaelis M, Kleinschmidt MC, Barth S, Rothweiler F, Geiler J, Breitling R, Mayer B, Deubzer H, Witt O, Kreuter J, Doerr HW, Cinatl J and Cinatl J Jr: Anti-cancer effects of artesunate in a panel of chemoresistant neuroblastoma cell lines. Biochem Pharmacol. 79:130–136. 2010. View Article : Google Scholar : PubMed/NCBI
17	Efferth T, Giaisi M, Merling A, Krammer PH and Li-Weber M: Artesunate induces ROS-mediated apoptosis in doxorubicin-resistant T leukemia cells. PLoS One. 2:e6932007. View Article : Google Scholar : PubMed/NCBI
18	Reungpatthanaphong P and Mankhetkorn S: Modulation of multidrug resistance by artemisinin, artesunate and dihydroartemisinin in K562/adr and GLC4/adr resistant cell lines. Biol Pharm Bull. 25:1555–1561. 2002. View Article : Google Scholar : PubMed/NCBI
19	Haufroid V: Genetic Polymorphisms of ATP-binding cassette transporters ABCB1 and ABCC2 and their impact on drug disposition. Curr Drug Targets. 12:631–646. 2011. View Article : Google Scholar : PubMed/NCBI
20	Shukla S, Ohnuma S and Ambudkar SV: Improving cancer chemotherapy with modulators of ABC drug transporters. Curr Drug Targets. 12:621–630. 2011. View Article : Google Scholar : PubMed/NCBI
21	Doyle LA, Yang W, Abruzzo LV, Krogmann T, Gao Y, Rishi AK and Ross DD: A multidrug resistance transporter from human MCF-7 breast cancer cells. Proc Natl Acad Sci USA. 95:15665–15670. 1998. View Article : Google Scholar : PubMed/NCBI
22	Li J, Li ZN, Du YJ, Li XQ, Bao QL and Chen P: Expression of MRP1, BCRP, LRP, and ERCC1 in advanced non-small-cell lung cancer: correlation with response to chemotherapy and survival. Clin Lung Cancer. 10:414–421. 2009. View Article : Google Scholar
23	Ni Z and Mao Q: ATP-binding cassette efflux transporters in human placenta. Curr Pharm Biotechnol. 12:674–685. 2011. View Article : Google Scholar : PubMed/NCBI
24	Poller B, Wagenaar E, Tang SC and Schinkel AH: Double-transduced MDCKII cells to study human P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2) interplay in drug transport across the blood-brain barrier. Mol Pharm. 8:571–582. 2011. View Article : Google Scholar