The online version of this article (doi:10.1186/1475-2867-12-35) contains supplementary material, which is available to authorized users.
The authors declare that they have no competing interests.
NS designed the study. MJ, WC performed experiments and data analysis, NS and MJ drafted the manuscript. NS, KY revised the manuscript. All authors read and approved the final manuscript.
Cisplatin resistance is a serious problem in cancer treatment. To overcome it, alternative approaches including virotherapy are being pursued. One of the candidates for anticancer virotherapy is the Newcastle disease virus (NDV). Even though NDV's oncolytic properties in various cancer cells have been widely reported, information regarding its effects on cisplatin resistant cancer cells is still limited. Therefore, we tested the oncolytic efficacy of a strain of NDV, designated as AF2240, in a cisplatin-resistant breast cancer cell line.
Cisplatin-resistant cell line (MCF7-CR) was developed from the MCF7 human breast adenocarcinoma cell line by performing a seven-cyclic exposure to cisplatin. Following NDV infection, fluorescence-activated cell sorting (FACS) analysis and immunoblotting were used to measure cell viability and viral protein expression, respectively. Production of virus progeny was then assessed by using the plaque assay technique.
Infection of a mass population of the MCF7-CR with NDV resulted in 50% killing in the first 12 hours post-infection (hpi), comparable to the parental MCF7. From 12 hpi onwards, the remaining MCF7-CR became less susceptible to NDV killing. This reduced susceptibility led to increased viral protein synthesis and virus progeny production. The reduction was also associated with a prolonged cell survival via stabilization of the survivin protein.
Our findings showed for the first time, the involvement of survivin in the reduction of NDV-induced oncolysis in a subpopulation of cisplatin-resistant cells. This information will be important towards improving the efficacy of NDV as an anticancer agent in drug resistant cancers.
Authors’ original file for figure 112935_2012_359_MOESM1_ESM.jpeg
Authors’ original file for figure 212935_2012_359_MOESM2_ESM.jpeg
Authors’ original file for figure 312935_2012_359_MOESM3_ESM.tiff
Authors’ original file for figure 412935_2012_359_MOESM4_ESM.tiff
Authors’ original file for figure 512935_2012_359_MOESM5_ESM.tiff
Persons DL, Yazlovitskaya EM, Cui W, Pelling JC: Cisplatin-induced activation of mitogen-activated protein kinases in ovarian carcinoma cells: inhibition of extracellular signal-regulated kinase activity increases sensitivity to cisplatin. Clin Cancer Res. 1999, 5: 1007-1014. PubMed
Nomura T, Yamasaki M, Nomura Y, Mimata H: Expression of the inhibitors of apoptosis proteins in cisplatin-resistant prostate cancer cells. Oncol Rep. 2005, 14: 993-997. PubMed
Othman F, Ideris A, Motalleb G, Eshak Z, Rahmat A: Oncolytic effect of Newcastle Disease Virus AF2240 strain on the MCF-7 breast cancer cell line. Yakhteh Med J. 2010, 12: 17-24.
Ishida N, Taira H, Omata T, Mizumoto K, Hattori S, Iwasaki K, Kawakita M: Sequence of 2,617 nucleotides from the 3' end of Newcastle disease virus genome RNA and the predicted amino acid sequence of viral NP protein. Nucleic Acids Res. 1986, 14: 6551-6564. 10.1093/nar/14.16.6551. PubMedCentralCrossRefPubMed
Ali R, Alabsi AM, Ali AM, Ainideris , Omar AR, Yousoff K: Apoptosis induction and cytolytic effects of newcastle disease virus strain Af2240 on DBTRG.05 mg brain tumor cell line. Int J Cancer Res. 2011, 7: 25-35. 10.3923/ijcr.2011.25.35. CrossRef
Lukyanova NY, Rusetskya NV, Tregubova NA, Chekhun VF: Molecular profile and cell cycle in MCF-7 cells resistant to cisplatin and doxorubicin. Exp Oncol. 2009, 31: 87-91. PubMed
Lazar I, Yaacov B, Shiloach T, Eliahoo E, Kadouri L, Lotem M, Perlman R, Zakay-Rones Z, Panet A, Ben-Yehuda D: The oncolytic activity of Newcastle disease virus NDV-HUJ on chemoresistant primary melanoma cells is dependent on the proapoptotic activity of the inhibitor of apoptosis protein Livin. J Virol. 2010, 84: 639-646. 10.1128/JVI.00401-09. PubMedCentralCrossRefPubMed
Sutherland RL, Hall RE, Taylor IW: Cell proliferation kinetics of MCF-7 human mammary carcinoma cells in culture and effects of tamoxifen on exponentially growing and plateau-phase cells. Cancer Res. 1983, 43: 3998-4006. PubMed
Emmett SR, Dove B, Mahoney L, Wurm T, Hiscox JA: The cell cycle and virus infection. Methods Mol Biol. 2005, 296: 197-218. PubMed
Kumar B, Yadav A, Lang JC, Cipolla M, Schmitt AC, Arradaza N, Teknos TN, Kumar P: YM155 reverses cisplatin resistance in head and neck cancer by decreasing cytoplasmic survivin levels. Mol Cancer Ther. 2012, Epub ahead of print
- Reduced Newcastle disease virus-induced oncolysis in a subpopulation of cisplatin-resistant MCF7 cells is associated with survivin stabilization
- BioMed Central
Neu im Fachgebiet Onkologie
e.Med Kampagnen-Visual, Mail Icon II