<?xml version="1.0" encoding="UTF-8"?>
<!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.3 20210610//EN" "JATS-journalpublishing1-3.dtd">
<article article-type="research-article" dtd-version="1.3" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xml:lang="ru"><front><journal-meta><journal-id journal-id-type="publisher-id">pmj</journal-id><journal-title-group><journal-title xml:lang="ru">Тихоокеанский медицинский журнал</journal-title><trans-title-group xml:lang="en"><trans-title>Pacific Medical Journal</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">1609-1175</issn><publisher><publisher-name>TGMU</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.34215/1609-1175-2025-2-50-54</article-id><article-id custom-type="elpub" pub-id-type="custom">pmj-2926</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="ru"><subject>ОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯ</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>ORIGINAL RESEARCHES</subject></subj-group></article-categories><title-group><article-title>Фармакологические мишени стволовых клеток глиобластомы</article-title><trans-title-group xml:lang="en"><trans-title>Pharmacological targets of glioblastoma stem cells</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-1312-8308</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Зайцев</surname><given-names>С. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Zaitsev</surname><given-names>S. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Зайцев Сергей Викторович – канд. биол. наук, зав. лабораторией молекулярной и клеточной нейробиологии департамента фармации и фармакологии Школы медицины и наук о жизни</p><p>690922, г. Владивосток, о. Русский, п. Аякс, 10</p></bio><bio xml:lang="en"><p>Sergey V. Zaitsev, Cand. Sci. (Biol.), Head of the Laboratory, Department of Pharmacy and Pharmacology, School of Medicine and Life Sciences</p><p>10 Ajax Bay, Russky Island, Vladivostok, 690922</p></bio><email xlink:type="simple">zaytcev.svi@dvfu.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Пугачева</surname><given-names>Е. С.</given-names></name><name name-style="western" xml:lang="en"><surname>Pugacheva</surname><given-names>E. S.</given-names></name></name-alternatives><bio xml:lang="ru"><p>690922, г. Владивосток, о. Русский, п. Аякс, 10</p></bio><bio xml:lang="en"><p>10 Ajax Bay, Russky Island, Vladivostok, 690922</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Косьянова</surname><given-names>А. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Kos'yanova</surname><given-names>A. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>690922, г. Владивосток, о. Русский, п. Аякс, 10</p></bio><bio xml:lang="en"><p>10 Ajax Bay, Russky Island, Vladivostok, 690922</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Пак</surname><given-names>О. И.</given-names></name><name name-style="western" xml:lang="en"><surname>Pak</surname><given-names>O. I.</given-names></name></name-alternatives><bio xml:lang="ru"><p>690922, г. Владивосток, о. Русский, п. Аякс, 10</p></bio><bio xml:lang="en"><p>10 Ajax Bay, Russky Island, Vladivostok, 690922</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Брюховецкий</surname><given-names>И. С.</given-names></name><name name-style="western" xml:lang="en"><surname>Bryukhovetskiy</surname><given-names>I. S.</given-names></name></name-alternatives><bio xml:lang="ru"><p>690922, г. Владивосток, о. Русский, п. Аякс, 10</p></bio><bio xml:lang="en"><p>10 Ajax Bay, Russky Island, Vladivostok, 690922</p></bio><xref ref-type="aff" rid="aff-2"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>Дальневосточный федеральный университет</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Eastern Federal University</institution><country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-2"><aff xml:lang="ru"><institution>Дальневосточный федеральный университет; Национальный научный центр морской биологии им. А.В. Жирмунского ДВО РАН</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Eastern Federal University; A.V. Zhirmunsky National Marine Biology Research Center</institution><country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2025</year></pub-date><pub-date pub-type="epub"><day>11</day><month>08</month><year>2025</year></pub-date><volume>0</volume><issue>2</issue><fpage>50</fpage><lpage>54</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Зайцев С.В., Пугачева Е.С., Косьянова А.А., Пак О.И., Брюховецкий И.С., 2025</copyright-statement><copyright-year>2025</copyright-year><copyright-holder xml:lang="ru">Зайцев С.В., Пугачева Е.С., Косьянова А.А., Пак О.И., Брюховецкий И.С.</copyright-holder><copyright-holder xml:lang="en">Zaitsev S.V., Pugacheva E.S., Kos'yanova A.A., Pak O.I., Bryukhovetskiy I.S.</copyright-holder><license xml:lang="ru" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>Данная работа распространяется под лицензией Creative Commons Attribution 4.0.</license-p></license><license xml:lang="en" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>This work is licensed under a Creative Commons Attribution 4.0 License.</license-p></license></permissions><self-uri xlink:href="https://www.tmj-vgmu.ru/jour/article/view/2926">https://www.tmj-vgmu.ru/jour/article/view/2926</self-uri><abstract><p>Цель: поиск фармакологических мишеней для повышения эффективности химиолучевой терапии. Материалы и методы: использован высокочувствительный транскриптомный анализ на микрочипах высокой плотности, рутинные клеточные технологии и современный биоинформационный анализ. Результаты: идентифицировано 677 генов CD133+ ОСК, усиливших экспрессию в 2 и более раз по сравнению с дифференцированными ОК (ДОК): выявлено 13 транскпиптов, критически усиливших уровень синтеза в ОСК (&gt; 4 раз): akt1, hdac1, cnnb1, ahnak2, daam, pik3cg, mctp1, Il31ra, ca9, csnk2b, col6a1, col6a3 и lambd1. Заключение: фармакологическими мишенями в ОСК являются белки АКТ1, HDAC1, CTNNB1 – продукты экспрессии генов akt1, hdac1, ctnnb1, к целям второго порядка следует отнести белковые продукты генов ahnak2, daam, pik3cg, mctp1, Il31ra, ca9, csnk2b, col6a1, col6a3 и lambd1</p></abstract><trans-abstract xml:lang="en"><p>Objective. To identify pharmacological targets to enhance the effectiveness of chemoradiotherapy. Materials and methods. A highly sensitive transcriptomic analysis using high-density microarrays, routine cell technologies, and advanced bioinformatic analysis were employed.  Results. A total of 677 genes were identified in CD133+ glioblastoma stem cells (GSCs) with expression levels increased by two-fold or more compared to differentiated glioblastoma cells (DGCs). Among them, 13 transcripts demonstrated a critically elevated expression in GSCs (more than 4-fold), including: akt1, hdac1, cnnb1, ahnak2, daam, pik3cg, mctp1, Il31ra, ca9, csnk2b, col6a1, col6a3 and lambd1. Conclusion. The primary pharmacological targets in glioblastoma stem cells (GSCs) are the proteins AKT1, HDAC1, and CTNNB1 – the products of the akt1, hdac1, and ctnnb1 genes. Secondary targets include the protein products of the ahnak2, daam, pik3cg, mctp1, il31ra, ca9, csnk2b, col6a1, col6a3, and lambd1 genes</p></trans-abstract><kwd-group xml:lang="ru"><kwd>глиобластома</kwd><kwd>опухолевые стволовые клетки</kwd><kwd>фармакологические мишени</kwd></kwd-group><kwd-group xml:lang="en"><kwd>glioblastoma</kwd><kwd>cancer stem cells</kwd><kwd>pharmacological targets</kwd></kwd-group><funding-group><funding-statement xml:lang="ru">Авторы заявляют о финансировании проведенного исследования из собственных средств</funding-statement></funding-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">Schaff LR, Mellinghoff IK. Glioblastoma and Other Primary Brain Malignancies in Adults: A Review. JAMA. 2023 Feb 21;329(7):574–587. doi: 10.1001/jama.2023.0023</mixed-citation><mixed-citation xml:lang="en">Schaff LR, Mellinghoff IK. Glioblastoma and Other Primary Brain Malignancies in Adults: A Review. JAMA. 2023 Feb 21;329(7):574–587. doi: 10.1001/jama.2023.0023</mixed-citation></citation-alternatives></ref><ref id="cit2"><label>2</label><citation-alternatives><mixed-citation xml:lang="ru">Sloan AR, Silver DJ, Kint S, Gallo M, Lathia JD. Cancer stem cell hypothesis 2.0 in glioblastoma: Where are we now and where are we going? Neuro Oncol. 2024 May 3;26(5):785–795. doi: 10.1093/neuonc/noae011</mixed-citation><mixed-citation xml:lang="en">Sloan AR, Silver DJ, Kint S, Gallo M, Lathia JD. Cancer stem cell hypothesis 2.0 in glioblastoma: Where are we now and where are we going? Neuro Oncol. 2024 May 3;26(5):785–795. doi: 10.1093/neuonc/noae011</mixed-citation></citation-alternatives></ref><ref id="cit3"><label>3</label><citation-alternatives><mixed-citation xml:lang="ru">Yabo YA, Niclou SP, Golebiewska A. Cancer cell heterogeneity and plasticity: A paradigm shift in glioblastoma. Neuro Oncol. 2022 May 4;24(5):669–682. doi: 10.1093/neuonc/noab269</mixed-citation><mixed-citation xml:lang="en">Yabo YA, Niclou SP, Golebiewska A. Cancer cell heterogeneity and plasticity: A paradigm shift in glioblastoma. Neuro Oncol. 2022 May 4;24(5):669–682. doi: 10.1093/neuonc/noab269</mixed-citation></citation-alternatives></ref><ref id="cit4"><label>4</label><citation-alternatives><mixed-citation xml:lang="ru">Kim KH, Migliozzi S, Koo H, Hong JH, Park SM, Kim S, Kwon HJ, Ha S, Garofano L, Oh YT, D'Angelo F, Kim CI, Kim S, Lee JY, Kim J, Hong J, Jang EH, Mathon B, Di Stefano AL, Bielle F, Laurenge A, Nesvizhskii AI, Hur EM, Yin J, Shi B, Kim Y, Moon KS, Kwon JT, Lee SH, Lee SH, Gwak HS, Lasorella A, Yoo H, Sanson M, Sa JK, Park CK, Nam DH, Iavarone A, Park JB. Integrated proteogenomic characterization of glioblastoma evolution. Cancer Cell. 2024 Mar 11;42(3):358–377.e8. doi: 10.1016/j.ccell.2023.12.015</mixed-citation><mixed-citation xml:lang="en">Kim KH, Migliozzi S, Koo H, Hong JH, Park SM, Kim S, Kwon HJ, Ha S, Garofano L, Oh YT, D'Angelo F, Kim CI, Kim S, Lee JY, Kim J, Hong J, Jang EH, Mathon B, Di Stefano AL, Bielle F, Laurenge A, Nesvizhskii AI, Hur EM, Yin J, Shi B, Kim Y, Moon KS, Kwon JT, Lee SH, Lee SH, Gwak HS, Lasorella A, Yoo H, Sanson M, Sa JK, Park CK, Nam DH, Iavarone A, Park JB. Integrated proteogenomic characterization of glioblastoma evolution. Cancer Cell. 2024 Mar 11;42(3):358–377.e8. doi: 10.1016/j.ccell.2023.12.015</mixed-citation></citation-alternatives></ref><ref id="cit5"><label>5</label><citation-alternatives><mixed-citation xml:lang="ru">Bryukhovetskiy I. Cell-based immunotherapy of glioblastoma multiforme. Oncol Lett. 2022 Apr;23(4):133. doi: 10.3892/ol.2022.13253</mixed-citation><mixed-citation xml:lang="en">Bryukhovetskiy I. Cell-based immunotherapy of glioblastoma multiforme. Oncol Lett. 2022 Apr;23(4):133. doi: 10.3892/ol.2022.13253</mixed-citation></citation-alternatives></ref><ref id="cit6"><label>6</label><citation-alternatives><mixed-citation xml:lang="ru">Srivastava R, Dodda M, Zou H, Li X, Hu B. Tumor Niches: Perspectives for Targeted Therapies in Glioblastoma. Antioxid Redox Signal. 2023 Nov;39(13–15):904–922. doi: 10.1089/ars.2022.0187</mixed-citation><mixed-citation xml:lang="en">Srivastava R, Dodda M, Zou H, Li X, Hu B. Tumor Niches: Perspectives for Targeted Therapies in Glioblastoma. Antioxid Redox Signal. 2023 Nov;39(13–15):904–922. doi: 10.1089/ars.2022.0187</mixed-citation></citation-alternatives></ref><ref id="cit7"><label>7</label><citation-alternatives><mixed-citation xml:lang="ru">Barzegar Behrooz A, Talaie Z, Jusheghani F, Łos MJ, Klonisch T, Ghavami S. Wnt and PI3K/Akt/mTOR Survival Pathways as Therapeutic Targets in Glioblastoma. Int J Mol Sci. 2022 Jan 25;23(3):1353. doi: 10.3390/ijms23031353</mixed-citation><mixed-citation xml:lang="en">Barzegar Behrooz A, Talaie Z, Jusheghani F, Łos MJ, Klonisch T, Ghavami S. Wnt and PI3K/Akt/mTOR Survival Pathways as Therapeutic Targets in Glioblastoma. Int J Mol Sci. 2022 Jan 25;23(3):1353. doi: 10.3390/ijms23031353</mixed-citation></citation-alternatives></ref><ref id="cit8"><label>8</label><citation-alternatives><mixed-citation xml:lang="ru">Manoranjan B, Chokshi C, Venugopal C, Subapanditha M, Savage N, Tatari N, Provias JP, Murty NK, Moffat J, Doble BW, Singh SK. A CD133-AKT-Wnt signaling axis drives glioblastoma brain tumor-initiating cells. Oncogene. 2020 Feb;39(7):1590– 1599. doi: 10.1038/s41388-019-1086-x</mixed-citation><mixed-citation xml:lang="en">Manoranjan B, Chokshi C, Venugopal C, Subapanditha M, Savage N, Tatari N, Provias JP, Murty NK, Moffat J, Doble BW, Singh SK. A CD133-AKT-Wnt signaling axis drives glioblastoma brain tumor-initiating cells. Oncogene. 2020 Feb;39(7):1590– 1599. doi: 10.1038/s41388-019-1086-x</mixed-citation></citation-alternatives></ref><ref id="cit9"><label>9</label><citation-alternatives><mixed-citation xml:lang="ru">Jung KH, Lee JH, Kim M, Lee EJ, Cho YS, Lee KH. Celecoxib- Induced Modulation of Colon Cancer CD133 Expression Occurs through AKT Inhibition and Is Monitored by 89Zr Immuno-PET. Mol Imaging. 2022 Jan 7;2022:4906934. doi: 10.1155/2022/4906934</mixed-citation><mixed-citation xml:lang="en">Jung KH, Lee JH, Kim M, Lee EJ, Cho YS, Lee KH. Celecoxib- Induced Modulation of Colon Cancer CD133 Expression Occurs through AKT Inhibition and Is Monitored by 89Zr Immuno-PET. Mol Imaging. 2022 Jan 7;2022:4906934. doi: 10.1155/2022/4906934</mixed-citation></citation-alternatives></ref><ref id="cit10"><label>10</label><citation-alternatives><mixed-citation xml:lang="ru">Liu DX, Hao SL, Yang WX. Crosstalk Between beta-CATENINMediated Cell Adhesion and the WNT Signaling Pathway. DNA Cell Biol. 2023 Jan;42(1):1–13. doi: 10.1089/dna.2022.0424</mixed-citation><mixed-citation xml:lang="en">Liu DX, Hao SL, Yang WX. Crosstalk Between beta-CATENINMediated Cell Adhesion and the WNT Signaling Pathway. DNA Cell Biol. 2023 Jan;42(1):1–13. doi: 10.1089/dna.2022.0424</mixed-citation></citation-alternatives></ref><ref id="cit11"><label>11</label><citation-alternatives><mixed-citation xml:lang="ru">Gopinathan A, Sankhe R, Rathi E, Kodi T, Upadhya R, Pai KSR, Kishore A. An in silico drug repurposing approach to identify HDAC1 inhibitors against glioblastoma. J Biomol Struct Dyn. 2024 Apr 30:1–14. doi: 10.1080/07391102.2024.2335293</mixed-citation><mixed-citation xml:lang="en">Gopinathan A, Sankhe R, Rathi E, Kodi T, Upadhya R, Pai KSR, Kishore A. An in silico drug repurposing approach to identify HDAC1 inhibitors against glioblastoma. J Biomol Struct Dyn. 2024 Apr 30:1–14. doi: 10.1080/07391102.2024.2335293</mixed-citation></citation-alternatives></ref><ref id="cit12"><label>12</label><citation-alternatives><mixed-citation xml:lang="ru">Zhang BT, Leung PC, Wong CK, Wang DJ. The Immunomodulatory Effects of Vitamin D on COVID-19 Induced Glioblastoma Recurrence via the PI3K-AKT Signaling Pathway. Int J Mol Sci. 2024 Dec 2;25(23):12952. doi: 10.3390ijms252312952</mixed-citation><mixed-citation xml:lang="en">Zhang BT, Leung PC, Wong CK, Wang DJ. The Immunomodulatory Effects of Vitamin D on COVID-19 Induced Glioblastoma Recurrence via the PI3K-AKT Signaling Pathway. Int J Mol Sci. 2024 Dec 2;25(23):12952. doi: 10.3390ijms252312952</mixed-citation></citation-alternatives></ref><ref id="cit13"><label>13</label><citation-alternatives><mixed-citation xml:lang="ru">Hashemi M, Etemad S, Rezaei S, Ziaolhagh S, Rajabi R, Rahmanian P, Abdi S, Koohpar ZK, Rafiei R, Raei B, Ahmadi F, Salimimoghadam S, Aref AR, Zandieh MA, Entezari M, Taheriazam A, Hushmandi K. Progress in targeting PTENPI3K/Akt axis in glioblastoma therapy: Revisiting molecular interactions. Biomed Pharmacother. 2023 Feb;158:114204. doi: 10.1016/j.biopha.2022.114204</mixed-citation><mixed-citation xml:lang="en">Hashemi M, Etemad S, Rezaei S, Ziaolhagh S, Rajabi R, Rahmanian P, Abdi S, Koohpar ZK, Rafiei R, Raei B, Ahmadi F, Salimimoghadam S, Aref AR, Zandieh MA, Entezari M, Taheriazam A, Hushmandi K. Progress in targeting PTENPI3K/Akt axis in glioblastoma therapy: Revisiting molecular interactions. Biomed Pharmacother. 2023 Feb;158:114204. doi: 10.1016/j.biopha.2022.114204</mixed-citation></citation-alternatives></ref><ref id="cit14"><label>14</label><citation-alternatives><mixed-citation xml:lang="ru">Zhang C, Wang M, Ji F, Peng Y, Wang B, Zhao J, Wu J, Zhao H. A Novel Glucose Metabolism-Related Gene Signature for Overall Survival Prediction in Patients with Glioblastoma. Biomed Res Int. 2021 Jan 22;2021:8872977. doi: 10.1155/2021/8872977</mixed-citation><mixed-citation xml:lang="en">Zhang C, Wang M, Ji F, Peng Y, Wang B, Zhao J, Wu J, Zhao H. A Novel Glucose Metabolism-Related Gene Signature for Overall Survival Prediction in Patients with Glioblastoma. Biomed Res Int. 2021 Jan 22;2021:8872977. doi: 10.1155/2021/8872977</mixed-citation></citation-alternatives></ref><ref id="cit15"><label>15</label><citation-alternatives><mixed-citation xml:lang="ru">Latour M, Her NG, Kesari S, Nurmemmedov E. WNT Signaling as a Therapeutic Target for Glioblastoma. Int J Mol Sci. 2021 Aug 5;22(16):8428. doi: 10.3390/ijms22168428</mixed-citation><mixed-citation xml:lang="en">Latour M, Her NG, Kesari S, Nurmemmedov E. WNT Signaling as a Therapeutic Target for Glioblastoma. Int J Mol Sci. 2021 Aug 5;22(16):8428. doi: 10.3390/ijms22168428</mixed-citation></citation-alternatives></ref></ref-list><fn-group><fn fn-type="conflict"><p>The authors declare that there are no conflicts of interest present.</p></fn></fn-group></back></article>
