Skip to main content
SpringerLink
Log in

The Effect of Therapy Regimen on Antitumor Efficacy of the Nanosomal Doxorubicin against Rat Glioblastoma 101.8

  • Published:
Bulletin of Experimental Biology and Medicine Aims and scope

One of the key problems of glioblastoma treatment is the low effectiveness of chemotherapeutic drugs. Incorporation of doxorubicin into PLGA nanoparticles allows increasing the antitumor effect of the cytostatics against experimental rat glioblastoma 101.8. Animal survival, tumor volume, and oncogene expression in tumor cells were compared after early (days 2, 5, and 8 after tumor implantation) and late (days 8, 11, and 14) start of the therapy. At late start, a significant increase in the expression of oncogenes Gdnf, Pdgfra, and Melk and genes determining the development of multidrug resistance Abcb1b and Mgmt was revealed. At early start of therapy, only the expression of oncogenes Gdnf, Pdgfra, and Melk was enhanced. Early start of treatment prolonged the survival time and increased tumor growth inhibition by 141.4 and 95.7%, respectively, in comparison with the untreated group; these differences were not observed in the group with late start of therapy. The results indicate that the time of initiation of therapy is a critical parameter affecting the antitumor efficacy of DOX-PLGA.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Delgado-López PD, Corrales-García EM. Survival in glioblastoma: a review on the impact of treatment modalities. Clin. Transl. Oncol. 2016;18(11):1062-1071. doi: https://doi.org/10.1007/s12094-016-1497-x

    Article  CAS  PubMed  Google Scholar 

  2. Pereverzeva E, Treschalin I, Treschalin M, Arantseva D, Ermolenko Y, Kumskova N, Maksimenko O, Balabanyan V, Kreuter J, Gelperina S. Toxicological study of doxorubicin-loaded PLGA nanoparticles for the treatment of glioblastoma. Int. J. Pharm. 2019;554:161-178. doi: https://doi.org/10.1016/j.ijpharm.2018.11.014

    Article  CAS  PubMed  Google Scholar 

  3. Kudelkina VV, Khalansky AS, Makarova OV, Tsvetkov IS, Kosyreva AM, Alekseeva AI, Shelkov AY, Maksimenko OO, Razzhivina VA, Gelperina SE. Comparative morphological and biochemical characteristics of the toxic effects of doxorubicin and nanosomal PLGA-doxorubicin form in the experimental glioblastoma treatment. Klin. Eksper. Morfol. 2021;10(1):58-65. Russian. doi: https://doi.org/10.31088/CEM2021.10.1.58-65

  4. Wen J, Chen W, Zhu Y, Zhang P. Clinical features associated with the efficacy of chemotherapy in patients with glioblastoma (GBM): a surveillance, epidemiology, and end results (SEER) analysis. BMC Cancer. 2021;21(1):81. doi: https://doi.org/10.1186/s12885-021-07800-0.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Lee EQ, Weller M, Sul J, Bagley SJ, Sahebjam S, van den Bent M, Ahluwalia M, Campian JL, Galanis E, Gilbert MR, Holdhoff M, Lesser GJ, Lieberman FS, Mehta MP, Penas-Prado M, Schreck KC, Strowd RE, Vogelbaum MA, Walbert T, Chang SM, Nabors LB, Grossman S, Reardon DA, Wen PY. Optimizing eligibility criteria and clinical trial conduct to enhance clinical trial participation for primary brain tumor patients. Neuro Oncol. 2020;22(5):601-612. doi: https://doi.org/10.1093/neuonc/noaa015

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Khalansky AS, Kondakova LI. Transplanted rat glioma 101.8.I. Biological characteristics. Klin. Eksper. Morfol. 2013;(4):63-68. Russian.

  7. Maksimenko O, Malinovskaya J, Shipulo E, Osipova N, Razzhivina V, Arantseva D, Yarovaya O, Mostovaya U, Khalansky A, Fedoseeva V, Alekseeva A, Vanchugova L, Gorshkova M, Kovalenko E, Balabanyan V, Melnikov P, Baklaushev V, Chekhonin V, Kreuter J, Gelperina S. Doxorubicin-loaded PLGA nanoparticles for the chemotherapy of glioblastoma: Towards the pharmaceutical development. Int. J. Pharm. 2019;572:118733. doi: https://doi.org/10.1016/j.ijpharm.2019.118733

    Article  CAS  PubMed  Google Scholar 

  8. Kim HJ, Kim W. Method of tumor volume evaluation using magnetic resonance imaging for outcome prediction in cervical cancer treated with concurrent chemotherapy and radiotherapy. Radiat. Oncol. J. 2012;30(2):70-77. doi: https://doi.org/10.3857/roj.2012.30.2.70

  9. Fedoseeva VV, Khalansky AS, Mkhitarov VA, Tsvetkov IS, Malinovskaya YA, Maksimenko OO, Gelperina SE, Balabanyan VY, Razzhivina VA, Gorelikov PL, Mikhailova LP, Makarova OV. Anti-tumor activity of doxorubicin-loaded poly(lactide-co-glycolide) nanoparticles in the experimental glioblastoma. Klin. Eksper. Morfol. 2017;(2):65-71. Russian.

  10. Seçil M, Çullu N, Aslan G, Mungan U, Uysal F, Tuna B, Yörükoğlu K. The effect of tumor volume on survival in patients with renal cell carcinoma. Diagn. Interv. Radiol. 2012;18(5):480-487. doi: https://doi.org/10.4261/1305-3825.DIR.5346-11.1

    Article  PubMed  Google Scholar 

  11. Zhang J, Gold KA, Lin HY, Swisher SG, Xing Y, Lee JJ, Kim ES, William WN Jr. Relationship between tumor size and survival in non-small-cell lung cancer (NSCLC): an analysis of the surveillance, epidemiology, and end results (SEER) registry. J. Thorac. Oncol. 2015;10(4):682-690. doi: https://doi.org/10.1097/JTO.0000000000000456

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Ball D, Mitchell A, Giroux D, Rami-Porta R; IASLC Staging Committee and Participating Institutions. Effect of tumor size on prognosis in patients treated with radical radiotherapy or chemoradiotherapy for non-small cell lung cancer. An analysis of the staging project database of the International Association for the Study of Lung Cancer. J. Thorac. Oncol. 2013;8(3):315-321. doi: https://doi.org/10.1097/JTO.0b013e31827dc74d

  13. Lee WY, Cheung CC, Liu KW, Fung KP, Wong J, Lai PB, Yeung JH. Cytotoxic effects of tanshinones from Salvia miltiorrhiza on doxorubicin-resistant human liver cancer cells. J. Nat. Prod. 2010;73(5):854-859. doi: https://doi.org/10.1021/np900792p

    Article  CAS  PubMed  Google Scholar 

  14. Podolski-Renić A, Jadranin M, Stanković T, Banković J, Stojković S, Chiourea M, Aljančić I, Vajs V, Tešević V, Ruždijić S, Gagos S, Tanić N, Pešić M. Molecular and cytogenetic changes in multi-drug resistant cancer cells and their influence on new compounds testing. Cancer Chemother. Pharmacol. 2013;72(3):683-697. doi: https://doi.org/10.1007/s00280-013-2247-1

    Article  CAS  PubMed  Google Scholar 

  15. Xu L, Duan H, Zou Y, Wang J, Liu H, Wang W, Zhu X, Chen J, Zhu C, Yin Z, Zhao X, Wang Q. Xihuang Pill-destabilized CD133/EGFR/Akt/mTOR cascade reduces stemness enrichment of glioblastoma via the down-regulation of SOX2. Phytomedicine. 2023;114:154764. doi: https://doi.org/10.1016/j.phymed.2023.154764

    Article  CAS  PubMed  Google Scholar 

  16. Yu W, Ren X, Hu C, Tan Y, Shui Y, Chen Z, Zhang L, Peng J, Wei Q. Glioma SOX2 expression decreased after adjuvant therapy. BMC Cancer. 2019;19(1):1087. doi: https://doi.org/10.1186/s12885-019-6292-y

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Chen M, Ba H, Lu C, Dai J, Sun J. Glial Cell Line-Derived Neurotrophic Factor (GDNF) promotes angiogenesis through the demethylation of the Fibromodulin (FMOD) promoter in glioblastoma. Med. Sci. Monit. 2018;24:6137-6143. doi: https://doi.org/10.12659/MSM.911669

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Ozawa T, Brennan CW, Wang L, Squatrito M, Sasayama T, Nakada M, Huse JT, Pedraza A, Utsuki S, Yasui Y, Tandon A, Fomchenko EI, Oka H, Levine RL, Fujii K, Ladanyi M, Holland EC. PDGFRA gene rearrangements are frequent genetic events in PDGFRA-amplified glioblastomas. Genes Dev. 2010;24(19):2205-2218. doi: https://doi.org/10.1101/gad.1972310

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Gai QJ, Fu Z, He J, Mao M, Yao XX, Qin Y, Lan X, Zhang L, Miao JY, Wang YX, Zhu J, Yang FC, Lu HM, Yan ZX, Chen FL, Shi Y, Ping YF, Cui YH, Zhang X, Liu X, Yao XH, Lv SQ, Bian XW, Wang Y. EPHA2 mediates PDGFA activity and functions together with PDGFRA as prognostic marker and therapeutic target in glioblastoma. Signal Transduct. Target. Ther. 2022;7(1):33. doi: https://doi.org/10.1038/s41392-021-00855-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Minata M, Gu C, Joshi K, Nakano-Okuno M, Hong C, Nguyen CH, Kornblum HI, Molla A, Nakano I. Multi-kinase inhibitor C1 triggers mitotic catastrophe of glioma stem cells mainly through MELK kinase inhibition. PLoS One. 2014;9(4):e92546. doi: https://doi.org/10.1371/journal.pone.0092546

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. A. P. Avtsyn Research Institute of Human Morphology, B. V. Pet-rovsky Russian Research Center of Surgery, Moscow, Russia

    A. I. Alekseeva, A. S. Khalansky, E. A. Miroshnichenko, A. D. Gerasimov, A. V. Sentyabreva, V. V. Kudelkina & A. M. Kosyreva

  2. Dmitry Mendeleev University of Chemical Technology of Russia, Moscow, Russia

    N. S. Osipova & S. E. Gelperina

  3. Faculty of Fundamental Medicine, M. V. Lo-monosov Moscow State University, Moscow, Russia

    M. V. Gulyaev

Authors
  1. A. I. Alekseeva
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A. S. Khalansky
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. E. A. Miroshnichenko
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. A. D. Gerasimov
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. A. V. Sentyabreva
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. V. V. Kudelkina
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. N. S. Osipova
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. M. V. Gulyaev
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. S. E. Gelperina
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. A. M. Kosyreva
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to A. I. Alekseeva.

Additional information

Translated from Kletochnye Tekhnologii v Biologii i Meditsine, No. 4, pp. 276-282, December, 2023

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Alekseeva, A.I., Khalansky, A.S., Miroshnichenko, E.A. et al. The Effect of Therapy Regimen on Antitumor Efficacy of the Nanosomal Doxorubicin against Rat Glioblastoma 101.8. Bull Exp Biol Med 176, 697–702 (2024). https://doi.org/10.1007/s10517-024-06092-1

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10517-024-06092-1

Keywords

Search

Navigation