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INDUCTION OF APOPTOSIS IN B16 MELANOMA CELLS UNDER THE ACTION OF DRUG CONTAINING TUMOR NECROSIS FACTOR ALPHA AS A PART OF VIRUS-LIKE PARTICLES IN VITRO

https://doi.org/10.21294/1814-4861-2020-19-4-99-104

Abstract

Aim: to evaluate the antitumor activity of the drug containing TNF-alpha and high-polymer double-stranded RNA (dsRNA) in the composition of virus-like particles (VLP-TNF-alpha) on B16-F10 melanoma cells.
Material and Methods. Analysis of the anti-proliferative effect of VLP-TNF-alpha as well as its components, TNFalpha and dsRNA, was carried out using the MTT -test. Apoptosis of melanoma cells was assessed by flow cytofluorimetry with FITC-annexin V.
Results. It was shown that the cytotoxic effect of the drug containing the combination of TNF-alpha and dsRNA on melanoma cells significantly exceeded the total cytotoxic effect of TNF-alpha or dsRNA alone (LD50 for combination drug was 0.05 μg/ml, TNF-alpha – 9.5 μg/ml, dsRNA>20 μg/ml).
Conclusion. The drug containing TNF-alpha and dsRNA molecules may be a promising drug for the treatment of malignant tumors, including melanoma.

About the Authors

E. A. Vyazovaya
Institute of Medical Biotechnology, State Research Center of Virology and Biotechnology «Vector»
Russian Federation

Elena A. Vyazovaya, MD, PhD, Senior Researcher, Department of Biological Research 

9, Khimzavodskaya Street, 633010-Berdsk



L. R. Lebedev
Institute of Medical Biotechnology, State Research Center of Virology and Biotechnology «Vector»
Russian Federation

Leonid R. Lebedev, MD, DSc, Head of the Laboratory of Nucleic Acids and Recombinant Proteins 

9, Khimzavodskaya Street, 633010-Berdsk



E. D. Danilenko
Institute of Medical Biotechnology, State Research Center of Virology and Biotechnology «Vector»
Russian Federation

Elena D. Danilenko, MD, PhD, Director 
Researcher ID (WOS): A-7083-2014. 

9, Khimzavodskaya Street, 633010-Berdsk



References

1. Bernardo A.R., Cosgaya J.M., Aranda A., Jiménez-Lara A.M. Synergy between RA and TLR3 promotes type I IFN-dependent apoptosis through upregulation of TRAIL pathway in breast cancer cells. Cell Death Dis. 2013 Jan 31; 4: e479. doi: 10.1038/cddis.2013.5.

2. Ketlinsky S.A., Simbirtsev A.S. Cytokines. Saint Peterburg, 2008. 552 p. (in Russian).

3. Lienard D., Ewalenko P., Delmotte J.J., Renard N., Lejeune F.J. High-dose recombinant tumor necrosis factor alpha in combination with interferon gamma and melphalan in isolation perfusion of the limbs for melanoma and sarcoma. J Clin Oncol. 1992 Jan; 10(1): 52–60. doi: 10.1200/JCO.1992.10.1.52.

4. Chubenko V.A. Immunotherapy is based on cytokines (IL-1, IL-2, FNO, CSF, IFN). Practical Oncology. 2016; 17(2): 99–109. (in Russian). doi: 10.31917/1702099.

5. Xu G., Gu H., Hu B., Tong F., Liu D., Yu X., Zheng Y., Gu J. PEGb-(PELG-g-PLL) nanoparticles as TNF-α nanocarriers: potential cerebral ischemia/reperfusion injury therapeutic applications. Int J Nanomedicine. 2017 Mar 23; 12: 2243–2254. doi: 10.2147/IJN.S130842.

6. Masycheva V.I., Lebedev L.R., Danilenko E.D., Sysoeva G.M., Gamaley S.G.; State Scientific Center of Virology and Biotechnology «Vector». An antitumor agent based on a nanoparticle carrying a recombinant tumor necrosis factor alpha. Patent No 2386447 of the Russian Federation, MKP A61K 38/19. № 2008140246/15; Publ. 04.20.10. (in Russian).

7. Chawla-Sarkar M., Leaman D.W., Borden E.C. Preferential induction of apoptosis by interferon (IFN)-beta compared with IFN-alpha2: correlation with TRAIL/Apo2L induction in melanoma cell lines. Clin Cancer Res. 2001 Jun; 7(6): 1821–31.

8. Dai X., Zhang J., Arfuso F., Chinnathambi A., Zayed M.E., Alharbi S.A., Kumar A.P., Ahn K.S., Sethi G. Targeting TNF-related apoptosis-inducing ligand (TRAIL) receptor by natural products as a potential therapeutic approach for cancer therapy. Exp Biol Med (Maywood). 2015 Jun; 240(6): 760–73. doi: 10.1177/1535370215579167.

9. Gantier M.P., Williams B.R. The response of mammalian cells to double-stranded RNA. Cytokine Growth Factor Rev. 2007 Oct-Dec; 18(5–6): 363–71. doi: 10.1016/j.cytogfr.2007.06.016.

10. Salaun B., Lebecque S., Matikainen S., Rimoldi D., Romero P. Toll-like receptor 3 expressed by melanoma cells as a target for therapy? Clin Cancer Res. 2007 Aug 1; 13(15 Pt 1): 456574. doi: 10.1158/1078-0432.CCR-07-0274.

11. Gamaley S.G., Danilenko E.D., Bateneva A.V., Lebedev L.R., Masycheva V.I. Pharmacokinetics of molecular construction for deposition and transportation of biologically active substances to target cells. Siberian Journal of Oncology. 2008; (3): 92–5. (in Russian).

12. Lebedev L.R., Alikin Yu.S., Roslyakova E.Y., Podgorny V.F., Dubinkina O.S., Azaev M.Sh. Isolation and purification of double stranded RNA from killer strain of yeast Saccharomyces cerevisiae. Russian Journal of Biopharmaceuticals. 2014; 6(6): 32–8. (in Russian).

13. Pustoshilova N.M., Kileva E.V., Denisova L.Ya., Shingareva N.V., Korobko V.G., Denisov L.A., Masycheva V.I., Sandakhchiev L.S., Kalinin Yu .T.; State Scientific Center of Virology and Biotechnology «Vector». A method of producing a recombinant human tumor necrosis factor. Patent No. 2144958 of the Russian Federation, MCP C12N 15/28. № 97106895; Publ. 01.27.00. (in Russian).

14. Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods. 1983 Dec 16; 65(1–2): 55–63. doi: 10.1016/0022-1759(83)90303-4.

15. Zhao Y., Liu H., Xu L., Guo B., Kalvakolanu D.V., Liu X., Hu J., Zhang D., Sun Y., Zhang L., Xu D., Zhao X. Synergistic Suppression of Melanoma Growth by a Combination of Natural dsRNA and Panaxadiolsaponins. J Interferon Cytokine Res. 2018 Sep; 38(9): 378–387. doi: 10.1089/jir.2018.0037.

16. Chawla-Sarkar M., Lindner D.J., Liu Y.F., Williams B.R., Sen G.C., Silverman R.H., Borden E.C. Apoptosis and interferons: role of interferonstimulated genes as mediators of apoptosis. Apoptosis. 2003 Jun; 8(3): 237–49. doi: 10.1023/a:1023668705040.

17. Coati I., Miotto S., Zanetti I., Alaibac M. Toll-like receptors and cutaneous melanoma. Oncol Lett. 2016; 12(5): 3655–3661. doi: 10.3892/ol.2016.5166.

18. Peine K.J., Bachelder E.M., Vangundy Z., Papenfuss T., Brackman D.J., Gallovic M.D., Schully K., Pesce J., Keane-Myers A., Ainslie K.M. Efficient delivery of the toll-like receptor agonists polyinosinic:polycytidylic acid and CpG to macrophages by acetalated dextran microparticles. Mol Pharm. 2013 Aug 5; 10(8): 2849–57. doi: 10.1021/mp300643d.


Review

For citations:


Vyazovaya E.A., Lebedev L.R., Danilenko E.D. INDUCTION OF APOPTOSIS IN B16 MELANOMA CELLS UNDER THE ACTION OF DRUG CONTAINING TUMOR NECROSIS FACTOR ALPHA AS A PART OF VIRUS-LIKE PARTICLES IN VITRO. Siberian journal of oncology. 2020;19(4):99-104. (In Russ.) https://doi.org/10.21294/1814-4861-2020-19-4-99-104

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ISSN 1814-4861 (Print)
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