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Article Open Access

Association between DNA methylation and multidrug resistance in human glioma SHG‑44 cells

  • Authors:
    • Jin Chen
    • Zhong‑Ye Xu
    • Feng Wang
  • View Affiliations / Copyright

    Affiliations: Department of Neurosurgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, P.R. China
    Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].
  • Pages: 43-52
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    Published online on: October 17, 2014
       https://doi.org/10.3892/mmr.2014.2690
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Abstract

The aim of the present study was to evaluate the association between DNA methylation and multidrug resistance (MDR) in glioma and identify novel effectors responsible for MDR in human gliomas. An MDR glioma cell line, SGH‑44/ADM, was developed using adriamycin (ADM) impulse treatment. Cryopreservation, recovery and withdrawal were performed to evaluate the stability of SGH‑44/ADM cells. The adherence rate and cellular morphology were observed by microscopy, and the cell growth curve and doubling time were determined. DNA methylation was analyzed using a methylated DNA immunoprecipitation microarray chip (MeDIP‑Chip). The cell cycle, Rh123 ingestion and exudation, and SGH‑44/ADM apoptosis were analyzed by flow cytometry. SGH‑44/ADM cells showed little difference as compared with parental cells, except that SGH‑44/ADM cells were bigger in size with a wizened nucleus. Compared to SGH‑44 cells, a larger proportion of SGH‑44/ADM cells remained in G1 and S phase, as measured by flow cytometry. The MDR of SGH‑44/ADM was associated with the upregulation of multi‑drug resistance 1, prostaglandin‑endoperoxide synthase 2 (COX‑2); protein kinase C α (PKCα); however, the expression of these genes was not associated with DNA methylation. In the MeDIP‑Chip analysis, 74 functions were markedly enhanced, and seven significant pathways were observed. Genes including SNAP47, ARRB2, PARD6B, TGFB1, VPS4B and CBLB were identified by gene ontology analysis. The predominant molecular mechanism of MDR in SGH‑44/ADM cells was identified as exocytosis and efflux. The expression of COX‑2, PKCα and P‑glycoprotein (Pgp) was not found to be associated with DNA methylation. Genes including SNAP47, VAMP4 and VAMP3 may serve as the downstream effectors of Pgp, COX‑2 or PKCα; however, further experiments are required to verify these observations.
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View References

1 

Mamelak AN and Jacoby DB: Targeted delivery of antitumoral therapy to glioma and other malignancies with synthetic chlorotoxin (TM-601). Expert Opin Drug Deliv. 4:175–186. 2007. View Article : Google Scholar : PubMed/NCBI

2 

Weiss RB: The anthracyclines: will we ever find a better doxorubicin? Semin Oncol. 19:670–686. 1992.PubMed/NCBI

3 

Minotti G, Menna P, Salvatorelli E, Cairo G and Gianni L: Anthracyclines: molecular advances and pharmacologic developments in antitumor activity and cardiotoxicity. Pharmacol Rev. 56:185–229. 2004. View Article : Google Scholar : PubMed/NCBI

4 

Peng X, Chen B, Lim CC and Sawyer DB: The cardiotoxicology of anthracycline chemotherapeutics: translating molecular mechanism into preventative medicine. Mol Interv. 5:163–171. 2005. View Article : Google Scholar : PubMed/NCBI

5 

Stewart LA: Chemotherapy in adult high-grade glioma: a systematic review and meta-analysis of individual patient data from 12 randomised trials. Lancet. 359:1011–1018. 2002. View Article : Google Scholar : PubMed/NCBI

6 

Lawson HC, Sampath P, Bohan E, et al: Interstitial chemotherapy for malignant gliomas: the Johns Hopkins experience. J Neurooncol. 83:61–70. 2007. View Article : Google Scholar : PubMed/NCBI

7 

Johannessen T-CA, Bjerkvig R and Tysnes BB: DNA repair and cancer stem-like cells - potential partners in glioma drug resistance? Cancer Treat Rev. 34:558–567. 2008. View Article : Google Scholar : PubMed/NCBI

8 

Bronger H, König J, Kopplow K, et al: ABCC drug efflux pumps and organic anion uptake transporters in human gliomas and the blood-tumor barrier. Cancer Res. 65:11419–11428. 2005. View Article : Google Scholar : PubMed/NCBI

9 

Calatozzolo C, Gelati M, Ciusani E, et al: Expression of drug resistance proteins Pgp, MRP1, MRP3, MRP5 and GST-pi in human glioma. J Neurooncol. 74:113–121. 2005. View Article : Google Scholar : PubMed/NCBI

10 

Dalton WS, Grogan TM, Meltzer PS, et al: Drug-resistance in multiple myeloma and non-Hodgkin’s lymphoma: detection of P-glycoprotein and potential circumvention by addition of verapamil to chemotherapy. J Clin Oncol. 7:415–424. 1989.

11 

Miller TP, Grogan TM, Dalton WS, et al: P-glycoprotein expression in malignant lymphoma and reversal of clinical drug resistance with chemotherapy plus high-dose verapamil. J Clin Oncol. 9:17–24. 1991.PubMed/NCBI

12 

Régina A, Demeule M, Laplante A, et al: Multidrug resistance in brain tumors: roles of the blood-brain barrier. Cancer Metastasis Rev. 20:13–25. 2001.PubMed/NCBI

13 

Mohri M, Nitta H and Yamashita J: Expression of multidrug resistance-associated protein (MRP) in human gliomas. J Neurooncol. 49:105–115. 2000. View Article : Google Scholar : PubMed/NCBI

14 

Spiegl-Kreinecker S, Buchroithner J, Elbling L, et al: Expression and functional activity of the ABC-transporter proteins P-glycoprotein and multidrug-resistance protein 1 in human brain tumor cells and astrocytes. J Neurooncol. 57:27–36. 2002. View Article : Google Scholar

15 

Herz J, Kowal RC, Goldstein JL and Brown MS: Proteolytic processing of the 600 kd low density lipoprotein receptor-related protein (LRP) occurs in a trans-Golgi compartment. EMBO J. 9:1769–1776. 1990.PubMed/NCBI

16 

Pinzón-Daza M, Garzón R, Courard P, et al: The association of statins plus LDL receptor-targeted liposome-encapsulated doxorubicin increases in vitro drug delivery across blood-brain barrier cells. Br J Pharmacol. 167:1431–1447. 2012.

17 

Ratnasinghe D, Daschner PJ, Anver MR, et al: Cyclooxygenase-2, P-glycoprotein-170 and drug resistance; is chemoprevention against multidrug resistance possible? Anticancer Res. 21:2141–2147. 2001.PubMed/NCBI

18 

Ali-Osman F, Caughlan J and Gray GS: Decreased DNA interstrand cross-linking and cytotoxicity induced in human brain tumor cells by 1,3-bis (2-chloroethyl)-1-nitrosourea after in vitro reaction with glutathione. Cancer Res. 49:5954–5958. 1989.PubMed/NCBI

19 

Chen C, Taniguchi T and D’Andrea A: The Fanconi anemia (FA) pathway confers glioma resistance to DNA alkylating agents. J Mol Med. 85:497–509. 2007. View Article : Google Scholar : PubMed/NCBI

20 

Wu XG, Peng SB and Huang Q: Transcriptional regulation of breast cancer resistance protein. Yi Chuan. 34:1529–1536. 2012.(In Chinese).

21 

Candelaria M, de la Cruz-Hernandez E, Taja-Chayeb L, et al: DNA methylation-independent reversion of gemcitabine resistance by hydralazine in cervical cancer cells. PLoS ONE. 7:e291812012. View Article : Google Scholar : PubMed/NCBI

22 

Ogawa T, Liggett TE, Melnikov AA, et al: Methylation of death-associated protein kinase is associated with cetuximab and erlotinib resistance. Cell Cycle. 11:1656–1663. 2012. View Article : Google Scholar : PubMed/NCBI

23 

He J: Expression of glioma stem cell marker CD133 and O6-methylguanine-DNA methyltransferase is associated with resistance to radiotherapy in gliomas. Oncol Rep. 26:1305–1313. 2011.PubMed/NCBI

24 

Wang B, Li Y, Tan Y, et al: Low-dose Cd induces hepatic gene hypermethylation, along with the persistent reduction of cell death and increase of cell proliferation in rats and mice. PLoS One. 7:e338532012. View Article : Google Scholar : PubMed/NCBI

25 

Kanehisa M, Goto S, Kawashima S, Okuno Y and Hattori M: The KEGG resource for deciphering the genome. Nucleic Acids Res. 32:D277–D280. 2004.PubMed/NCBI

26 

Yi M, Horton JD, Cohen JC, Hobbs HH and Stephens RM: WholePathwayScope: a comprehensive pathway-based analysis tool for high-throughput data. BMC Bioinformatics. 7:302006. View Article : Google Scholar : PubMed/NCBI

27 

Draghici S, Khatri P, Tarca AL, et al: A systems biology approach for pathway level analysis. Genome res. 17:1537–1545. 2007. View Article : Google Scholar : PubMed/NCBI

28 

Gene Ontology Consortium. The Gene Ontology (GO) project in 2006. Nucleic Acids Res. 34:D322–D326. 2006. View Article : Google Scholar : PubMed/NCBI

29 

Ashburner M, Ball CA, Blake JA, et al: Gene ontology: tool for the unification of biology. The Gene Ontology Consortium. Nat Genet. 25:25–29. 2000. View Article : Google Scholar : PubMed/NCBI

30 

Dupuy D, Bertin N, Hidalgo CA, et al: Genome-scale analysis of in vivo spatiotemporal promoter activity in Caenorhabditis elegans. Nat Biotechnol. 25:663–668. 2007. View Article : Google Scholar : PubMed/NCBI

31 

Schlitt T, Palin K, Rung J, et al: From gene networks to gene function. Genome Res. 13:2568–2576. 2003. View Article : Google Scholar : PubMed/NCBI

32 

Kim Y-J, Sah RLY, Doong J-YH and Grodzinsky AJ: Fluorometric assay of DNA in cartilage explants using Hoechst 33258. Anal Biochem. 174:168–176. 1988. View Article : Google Scholar : PubMed/NCBI

33 

Zhang B, Kirov S and Snoddy J: WebGestalt: an integrated system for exploring gene sets in various biological contexts. Nucleic Acids Res. 33:W741–W7748. 2005. View Article : Google Scholar : PubMed/NCBI

34 

Wang J, Duncan D, Shi Z and Zhang B: WEB-based GEne SeT AnaLysis Toolkit (WebGestalt): update 2013. Nucleic Acids Res. 41:W77–W7783. 2013. View Article : Google Scholar : PubMed/NCBI

35 

Denecke J, Fiedler K, Hacker-Klom U, et al: Multiple drug-resistant C6 glioma cells cross-resistant to irradiation. Anticancer Res. 17:4531–4534. 1997.PubMed/NCBI

36 

Shi L, Chen J, Yang J, et al: MiR-21 protected human glioblastoma U87MG cells from chemotherapeutic drug temozolomide induced apoptosis by decreasing Bax/Bcl-2 ratio and caspase-3 activity. Brain Res. 1352:255–264. 2010. View Article : Google Scholar : PubMed/NCBI

37 

Wang L, Xiong Y, Sun Y, et al: HLungDB: an integrated database of human lung cancer research. Nucleic Acids Res. 38:D665–D669. 2010. View Article : Google Scholar : PubMed/NCBI

38 

Kang MK and Kang SK: Tumorigenesis of chemotherapeutic drug-resistant cancer stem-like cells in brain glioma. Stem Cells Dev. 16:837–847. 2007. View Article : Google Scholar : PubMed/NCBI

39 

Sorokin A: Cyclooxygenase-2: potential role in regulation of drug efflux and multidrug resistance phenotype. Current Pharmaceutical Design. 10:647–657. 2004. View Article : Google Scholar : PubMed/NCBI

40 

Fan Q-W, Cheng C, Knight ZA, et al: EGFR signals to mTOR through PKC and independently of Akt in glioma. Sci Signal. 2:ra42009.PubMed/NCBI

41 

Basu A: PKC and resistance to chemotherapeutic agents. Protein Kinase C in Cancer Signaling and Therapy. Kazanietz MG: Humana Press; pp. 409–429. 2010, View Article : Google Scholar

42 

Leirdal M and Sioud M: Ribozyme inhibition of the protein kinase C alpha triggers apoptosis in glioma cells. Br J Cancer. 80:1558–1564. 1999. View Article : Google Scholar : PubMed/NCBI

43 

Fujita H, Yamanaka M, Imamura K, et al: A dominant negative form of the AAA ATPase SKD1/VPS4 impairs membrane trafficking out of endosomal/lysosomal compartments: class E vps phenotype in mammalian cells. J Cell Sci. 116:401–414. 2003. View Article : Google Scholar

44 

Schnitzer JE, Liu J and Oh P: Endothelial caveolae have the molecular transport machinery for vesicle budding, docking, and fusion including VAMP, NSF, SNAP, annexins, and GTPases. J Biol Chem. 270:14399–14404. 1995. View Article : Google Scholar : PubMed/NCBI

45 

Kawano M, Kumagai K, Nishijima M and Hanada K: Efficient trafficking of ceramide from the endoplasmic reticulum to the Golgi apparatus requires a VAMP-associated protein-interacting FFAT motif of CERT. J Biol Chem. 281:30279–30288. 2006. View Article : Google Scholar

46 

Guizetti J and Gerlich DW: ESCRT-III polymers in membrane neck constriction. Trends Cell Biol. 22:133–140. 2012. View Article : Google Scholar : PubMed/NCBI

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Spandidos Publications style
Chen J, Xu ZY and Wang F: Association between DNA methylation and multidrug resistance in human glioma SHG‑44 cells. Mol Med Rep 11: 43-52, 2015.
APA
Chen, J., Xu, Z., & Wang, F. (2015). Association between DNA methylation and multidrug resistance in human glioma SHG‑44 cells. Molecular Medicine Reports, 11, 43-52. https://doi.org/10.3892/mmr.2014.2690
MLA
Chen, J., Xu, Z., Wang, F."Association between DNA methylation and multidrug resistance in human glioma SHG‑44 cells". Molecular Medicine Reports 11.1 (2015): 43-52.
Chicago
Chen, J., Xu, Z., Wang, F."Association between DNA methylation and multidrug resistance in human glioma SHG‑44 cells". Molecular Medicine Reports 11, no. 1 (2015): 43-52. https://doi.org/10.3892/mmr.2014.2690
Copy and paste a formatted citation
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Spandidos Publications style
Chen J, Xu ZY and Wang F: Association between DNA methylation and multidrug resistance in human glioma SHG‑44 cells. Mol Med Rep 11: 43-52, 2015.
APA
Chen, J., Xu, Z., & Wang, F. (2015). Association between DNA methylation and multidrug resistance in human glioma SHG‑44 cells. Molecular Medicine Reports, 11, 43-52. https://doi.org/10.3892/mmr.2014.2690
MLA
Chen, J., Xu, Z., Wang, F."Association between DNA methylation and multidrug resistance in human glioma SHG‑44 cells". Molecular Medicine Reports 11.1 (2015): 43-52.
Chicago
Chen, J., Xu, Z., Wang, F."Association between DNA methylation and multidrug resistance in human glioma SHG‑44 cells". Molecular Medicine Reports 11, no. 1 (2015): 43-52. https://doi.org/10.3892/mmr.2014.2690
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