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DOI 10.34014/2227-1848-2021-3-129-140
EFFECT OF DIABETES MELLITUS ON THE LEVEL OF GROWTH FACTORS IN GUERIN CARCINOMA IN RATS OF BOTH SEXES
E.M. Frantsiyants, V.A. Bandovkina, I.V. Kaplieva, E.I. Surikova, I.V. Neskubina, L.K. Trepitaki, N.D. Cheryarina, Yu.A. Pogorelova, L.A. Nemashkalova, A.I. Shikhlyarova, I.M. Kotieva, M.I. Morozova
National Medical Research Center of Oncology, Ministry of Health of the Russian Federation, Rostov-on-Don, Russia
Diabetes mellitus is an independent risk factor for a number of malignant diseases. It is associated with increased mortality from cancer. The role of growth factors in the pathophysiology of diabetes mellitus and malignant tumors is dual and not fully defined.
The aim of the study was to examine the level of some growth factors and their receptors in the tissue of Guerin carcinoma and its perifocal zone growing in rats of both sexes with diabetes mellitus.
Materials and Methods. The authors determined the content of VEGF-A, VEGF-C their receptors sVEGF-R1 and sVEGF-R3, EGF and sEGF-R, TGFβ1 and sTGFβ1-R2, TNFα and sTNFα-R1, FGF21 in the samples of the tumor and the perifocal zone of Guerin carcinoma in nonlinear white rats of both sexes with diabetes mellitus (main group). ELISA test was used for this purpose. The control group consisted of animals with Guerin carcinoma without comorbid pathology.
Results. Tumors in female rats (main group) had a higher content of VEGF-C, EGF, TNFα and FGF21, VEGF-C/VEGF-R3, but a lower TGFβ1 level. In the perifocal zone these indicators, except TNFα, were lower than in the control group. In males (main group), TNFα and VEGF-A/VEGF-R1 levels in the tumor were higher. The content of VEGF-C, EGF, EGF-R and TGFβ1 was lower than in the control. At the same time, all the studied parameters were lower in the perifocal zone, except FGF21 and EGF-R.
Conclusion. Diabetes mellitus as a concomitant disease decreased the life expectancy of animals of both sexes with Guerin carcinoma. At the same time, high ratios of VEGF-A/VEGF-R1 in males, and VEGF-C/VEGF-R3, EGF/sEGF-R, and FGF21 in females in tumor samples were accompanied by the tumor growth in males and activation of metastatic processes in females.
Key words: Guerin carcinoma, diabetes mellitus, rats, growth factors, receptors.
Conflict of interest. The authors declare no conflict of interest.
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Received July 01, 2021; accepted August 08, 2021.
Information about the authors
Frantsiyants Elena Mikhaylovna, Doctor of Science (Biology), Professor, National Medical Research Center of Oncology. 344037, Russia, Rostov-on-Don, 14-ya liniya St., 63; e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it., ORCID: http://orcid.org/0000-0003-3618-6890
Bandovkina Valeriya Akhtyamovna, Doctor of Science (Biology), National Medical Research Center of Oncology. 344037, Russia, Rostov-on-Don, 14-ya liniya St., 63; e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it., ORCID: http://orcid.org/0000-0002-2302-8271
Kaplieva Irina Viktorovna, Doctor of Science (Medicine), National Medical Research Center of Oncology. 344037, Russia, Rostov-on-Don, 14-ya liniya St., 63; e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it., ORCID: http://orcid.org/0000-0002-3972-2452
Surikova Ekaterina Igorevna, Candidate of Science (Biology), National Medical Research Center of Oncology. 344037, Russia, Rostov-on-Don, 14-ya liniya St., 63; e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it., ORCID: http://orcid.org/0000-0002-4318-7587
Neskubina Irina Valer'evna, Candidate of Science (Biology), National Medical Research Center of Oncology. 344037, Russia, Rostov-on-Don, 14-ya liniya St., 63; e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it., ORCID ID: https://orcid.org/0000-0002-7395-3086
Trepitaki Lidiya Konstantinovna, Junior Researcher, National Medical Research Center of Oncology. 344037, Russia, Rostov-on-Don, 14-ya liniya St., 63; e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it., ORCID ID: http://orcid.org/0000-0002-9749-2747
Cheryarina Natal'ya Dmitrievna, Doctor-Laboratory Assistant, National Medical Research Center of Oncology. 344037, Russia, Rostov-on-Don, 14-ya liniya St., 63; e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it., ORCID: http://orcid.org/0000-0002-3711-8155
Pogorelova Yuliya Aleksandrovna, Candidate of Science (Biology), National Medical Research Center of Oncology. 344037, Russia, Rostov-on-Don, 14-ya liniya St., 63; e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it., ORCID: http://orcid.org/0000-0002-2674-9832
Nemashkalova Lyudmila Anatol'evna, Researcher, National Medical Research Center of Oncology. 344037, Russia, Rostov-on-Don, 14-ya liniya St., 63; e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it., ORCID ID: https://orcid.org/0000-0003-2713-8598.
Shikhlyarova Alla Ivanovna, Doctor of Science (Biology), Professor, National Medical Research Center of Oncology. 344037, Russia, Rostov-on-Don, 14-ya liniya St., 63; e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it., ORCID ID: https://orcid.org/0000-0003-2943-7655
Kotieva Inga Movlievna, Doctor of Science (Medicine), National Medical Research Center of Oncology. 344037, Russia, Rostov-on-Don, 14-ya liniya St., 63; e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it., ORCID ID: https://orcid.org/0000-0003-0252-4708
Morozova Mariya Igorevna, Physician, National Medical Research Center of Oncology. 344037, Russia, Rostov-on-Don, 14-ya liniya St., 63; e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it., ORCID ID: https://orcid.org/0000-0001-7640-6021
For citation
Frantsiyants E.M., Bandovkina V.A., Kaplieva I.V., Surikova E.I., Neskubina I.V., Trepitaki L.K., Cheryarina N.D., Pogorelova Yu.A., Nemashkalova L.A., Shikhlyarova A.I., Kotieva I.M., Morozova M.I. Vliyanie sakharnogo diabeta na uroven' faktorov rosta v kartsinome Gerena u krys oboego pola [Effect of diabetes mellitus on the level of growth factors in Guerin carcinoma in rats of both sexes]. Ul'yanovskiy mediko-biologicheskiy zhurnal. 2021; 3: 129–140. DOI: 10.34014/2227-1848-2021-3-129-140 (in Russian).
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УДК 616.43:[616.006:591.134.1]:616-092.9
DOI 10.34014/2227-1848-2021-3-129-140
ВЛИЯНИЕ САХАРНОГО ДИАБЕТА НА УРОВЕНЬ ФАКТОРОВ РОСТА В КАРЦИНОМЕ ГЕРЕНА У КРЫС ОБОЕГО ПОЛА
Е.М. Франциянц, В.А. Бандовкина, И.В. Каплиева, Е.И. Сурикова, И.В. Нескубина, Л.К. Трепитаки, Н.Д. Черярина, Ю.А. Погорелова, Л.А. Немашкалова, А.И. Шихлярова, И.М. Котиева, М.И. Морозова
ФГБУ «Национальный медицинский исследовательский центр онкологии» Министерства здравоохранения Российской Федерации, г. Ростов-на-Дону, Россия
Сахарный диабет является самостоятельным фактором риска возникновения ряда злокачественных заболеваний и связан с повышенной смертностью от рака. Роль факторов роста в патофизиологии сахарного диабета и злокачественных опухолей двойственна и до конца не определена.
Целью настоящего исследования явилось изучение уровня некоторых факторов роста и их рецепторов в ткани карциномы Герена, растущей на фоне сахарного диабета, и ее перифокальной зоне у крыс обоего пола.
Материалы и методы. У нелинейных белых крыс обоего пола в образцах опухоли и перифокальной зоны карциномы Герена, растущей на фоне сахарного диабета (основная группа), методом ИФА определяли содержание VEGF-A, VEGF-C и их рецепторов sVEGF-R1 и sVEGF-R3, EGF и sEGF-R, TGFβ1 и sTGFβ1-R2, TNFα и sTNFα-R1, FGF21. В качестве контрольной группы выступали животные с карциномой Герена без коморбидной патологии.
Результаты. У самок крыс основной группы в опухоли было выше содержание VEGF-C, EGF, TNFα и FGF21, VEGF-С/VEGF-R3, но ниже уровень TGFβ1, в перифокальной зоне эти показатели, за исключением TNFα, были ниже, чем в группе контроля. У самцов основной группы в опухоли был выше уровень TNFα и VEGF-A/VEGF-R1, содержание VEGF-C, EGF, EGF-R и TGFβ1 оказалось ниже, чем в контроле. При этом в перифокальной зоне все исследованные показатели были ниже, за исключением FGF21 и EGF-R.
Выводы. Сахарный диабет как сопутствующее злокачественному росту заболевание способствовал снижению продолжительности жизни животных обоего пола с карциномой Герена. При этом высокие в образцах опухоли соотношения VEGF-A/VEGF-R1 у самцов, VEGF-С/VEGF-R3, EGF/sEGF-R и FGF21 у самок сопровождались ростом объемов опухоли у самцов и активацией метастатических процессов у самок.
Ключевые слова: карцинома Герена, сахарный диабет, крысы, факторы роста, рецепторы.
Литература
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Sacerdote C., Ricceri F. Epidemiological dimensions of the association between type 2 diabetes and cancer: a review of observational studies. Diabetes Res. Clin. Pract. 2018; 143: 369–377. DOI: 10.1016/j.diabres.2018.03.002.
-
Suh S., Kim K.W. Diabetes and Cancer: Cancer Should Be Screened in Routine Diabetes Assessment. Diabetes Metab. J. 2019; 43 (6): 733–743. DOI: 10.4093/dmj.2019.0177.
-
Noto H. Unfolding link between diabetes and cancer. J. Diabetes Investig. 2018; 9: 473–474. DOI: 10.1111/jdi.12725.
-
Lugano R., Ramachandran M., Dimberg A. Tumor angiogenesis: causes, consequences, challenges and opportunities. Cellular and Molecular Life Sciences. 2020; 77 (9): 1745–1770. DOI: 10.1007/s00018-019-03351-7.
-
Nardi G.M., Ferrara E., Converti I., Cesarano F., Scacco S., Roberta Grassi, Antonio Gnoni, Felice Roberto Grassi, Biagio Rapone. Does Diabetes Induce the Vascular Endothelial Growth Factor (VEGF) Expression in Periodontal Tissues? A Systematic Review Int. J. Environ. Res. Public. Health. 2020; 17 (8): 2765. DOI: 10.3390/ijerph17082765.
-
Wang K., Dai X., He J., Yan X., Yang C., Fan X., Sun S., Chen J., Xu J., Deng Z., Fan J., Yuan X., Liu H., Carlson E.C, Shen F., Wintergerst K.A., Conklin D.J., Epstein P.N., Lu C., Tan Y. Endothelial Overexpression of Metallothionein Prevents Diabetes-Induced Impairment in Ischemia Angiogenesis Through Preservation of HIF-1alpha/SDF-1/VEGF Signaling in Endothelial Progenitor Cells. Diabetes. 2020; 69 (8): 1779–1792. DOI: 10.2337/db19-0829.
-
Arima M., Nakao S., Yamaguchi M., Feng H., Fujii Y., Shibata K., Wada I., Kaizu Y., Ahmadieh H., Ishibashi T., Stitt A.W., Sonoda K.H. Claudin-5 Redistribution Induced by Inflammation Leads to Anti-VEGF-Resistant Diabetic Macular Edema. Diabetes. 2020; 69 (5): 981–999. DOI: 10.2337/db19-1121.
-
Okonkwo U.A., Chen L., Ma D., Haywood V.A., Barakat M., Urao N., DiPietro L.A. Compromised angiogenesis and vascular Integrity in impaired diabetic wound healing. PLoS One. 2020; 15 (4): e0231962. DOI: 10.1371/journal.pone.0231962.
-
Di Venere D., Corsalini M., Nardi G.M., Laforgia A., Grassi F.R., Rapone B., Pettini F. Obstructive site localization in patients with Obstructive Sleep Apnea Syndrome: A comparison between otolaryngologic data and cephalometric values. Oral Implantol. 2017; 10: 295–310. DOI: 10.11138/orl/2017.10.3.295.
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Кит О.И., Франциянц Е.М., Бандовкина В.А., Каплиева И.В., Трепитаки Л.К., Розенко Л.Я., Черярина Н.Д., Погорелова Ю.А., Шульга А.В. Содержание факторов роста и их рецепторов в интактной и патологически измененной коже самок мышей в динамике роста злокачественной меланомы. Российский онкологический журнал. 2017; 22 (5): 281–287.
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Wu S.F., Noren Hooten N., Freeman D.W., Mode N.A., Zonderman A.B., Evans M.K. Extracellular vesicles in diabetes mellitus induce alterations in endothelial cell morphology and migration. J. Transl. Med. 2020; 18 (1): 230. DOI: 10.1186/s12967-020-02398-6.
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Le X., Nilsson M., Goldman J., Reck M., Nakagawa K., Kato T., Ares L.P., Frimodt-Moller B., Wolff K., Visseren-Grul C., Heymach J.V., Garon E.B. Dual EGFR-VEGF Pathway Inhibition: A Promising Strategy for Patients With EGFR-Mutant NSCLC. J. Thorac. Oncol. 2021; 16 (2): 205–215. DOI: 10.1016/j.jtho.2020.10.006.
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Jia J., Wei W., Yu F., Liu R., Shen Y., Zhang R., Yuan G., Zhou H. Circulating levels of fibroblast growth factor 21 in gestational diabetes mellitus: a meta-analysis. Endocr. J. 2021; 68 (3): 345–352. DOI: 10.1507/endocrj.EJ20-0481.
-
Huang H., Luo L., Liu Z., Li Y., Tong Z., Liu Z. Role of TNF-alpha and FGF-2 in the Fracture Healing Disorder of Type 2 Diabetes Model Induced by High Fat Diet Followed by Streptozotocin. Diabetes Metab. Syndr. Obes. 2020; 13: 2279–2288. DOI: 10.2147/DMSO.S23173.
-
Heydarpour F., Sajadimajd S., Haratipour P., Joshi T., Farzaei M.H., Khan H., Echeverría J. Involvement of TGF-β and Autophagy Pathways in Pathogenesis of Diabetes: A Comprehensive Review on Biological and Pharmacological Insights. Front. Pharmacol. 2020; 11: 498758. DOI: 10.3389/fphar.2020.498758.
-
Zhao M., Mishra L., Deng C.-X. The role of TGF-β/SMAD4 signaling in cancer. Int. J. Biol. Sci. 2018; 14: 111–123. DOI: 10.7150/ijbs.23230.
-
Lin P.P. Aneuploid Circulating Tumor-Derived Endothelial Cell (CTEC): A Novel Versatile Player in Tumor Neovascularization and Cancer Metastasis. Cells. 2020; 9 (6): 1539. DOI: 10.3390/cells9061539.
-
Bates D.O. Vascular endothelial growth factors and vascular permeability. Cardiovasc. Res. 2010; 87: 262–271. DOI: 10.1093/cvr/cvq105.
-
Ntellas P., Leonidas Mavroeidis, Stefania Gkoura, Ioanna Gazouli, Anna-Lea Amylidi, Alexandra Papadaki, George Zarkavelis, Davide Mauri, Georgia Karpathiou, Evangelos Kolettas, Anna Batistatou, George Pentheroudakis. Old Player-New Tricks: Non Angiogenic Effects of the VEGF/VEGFR Pathway in Cancer. Cancers (Basel). 2020; 12 (11): 3145. DOI: 10.3390/cancers12113145.
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Gloger M., Menzel L., Grau M., Vion A.C., Anagnostopoulos I., Zapukhlyak M., Gerlach K., Kammertöns T., Hehlgans T., Zschummel M., Lenz G., Gerhardt H., Höpken U.E., Rehm A. Lymphoma Angiogenesis Is Orchestrated by Noncanonical Signaling Pathways. Cancer Res. 2020; 80 (6): 1316–1329. DOI: 10.1158/0008-5472.CAN-19-1493.
Поступила в редакцию 01.07.2021; принята 06.08.2021.
Авторский коллектив
Франциянц Елена Михайловна – доктор биологических наук, профессор, ФГБУ «Национальный медицинский исследовательский центр онкологии» МЗ РФ. 344037, Россия, г. Ростов-на-Дону, ул. 14-я линия, 63; e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it., ORCID: http://orcid.org/0000-0003-3618-6890
Бандовкина Валерия Ахтямовна – доктор биологических наук, ФГБУ «Национальный медицинский исследовательский центр онкологии» МЗ РФ. 344037, Россия, г. Ростов-на-Дону, ул. 14-я линия, 63; e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it., ORCID: http://orcid.org/0000-0002-2302-8271
Каплиева Ирина Викторовна – доктор медицинских наук, ФГБУ «Национальный медицинский исследовательский центр онкологии» МЗ РФ. 344037, Россия, г. Ростов-на-Дону, ул. 14-я линия, 63; e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it., ORCID: http://orcid.org/0000-0002-3972-2452
Сурикова Екатерина Игоревна – кандидат биологических наук, ФГБУ «Национальный медицинский исследовательский центр онкологии» МЗ РФ. 344037, Россия, г. Ростов-на-Дону, ул. 14-я линия, 63; e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it., ORCID: http://orcid.org/0000-0002-4318-7587
Нескубина Ирина Валерьевна – кандидат биологических наук, ФГБУ «Национальный медицинский исследовательский центр онкологии» МЗ РФ. 344037, Россия, г. Ростов-на-Дону, ул. 14-я линия, 63; e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it., ORCID ID: https://orcid.org/0000-0002-7395-3086
Трепитаки Лидия Константиновна – младший научный сотрудник, ФГБУ «Национальный медицинский исследовательский центр онкологии» МЗ РФ. 344037, Россия, г. Ростов-на-Дону, ул. 14-я линия, 63; e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it., ORCID ID: http://orcid.org/0000-0002-9749-2747
Черярина Наталья Дмитриевна – врач-лаборант, ФГБУ «Национальный медицинский исследовательский центр онкологии» МЗ РФ. 344037, Россия, г. Ростов-на-Дону, ул. 14-я линия, 63; e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it., ORCID: http://orcid.org/0000-0002-3711-8155
Погорелова Юлия Александровна – кандидат биологических наук, ФГБУ «Национальный медицинский исследовательский центр онкологии» МЗ РФ. 344037, Россия, г. Ростов-на-Дону, ул. 14-я линия, 63; e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it., ORCID: http://orcid.org/0000-0002-2674-9832
Немашкалова Людмила Анатольевна – научный сотрудник, ФГБУ «Национальный медицинский исследовательский центр онкологии» МЗ РФ. 344037, Россия, г. Ростов-на-Дону, ул. 14-я линия, 63; e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it., ORCID ID: https://orcid.org/0000-0003-2713-8598
Шихлярова Алла Ивановна – доктор биологических наук, профессор, ФГБУ «Национальный медицинский исследовательский центр онкологии» МЗ РФ. 344037, Россия, г. Ростов-на-Дону, ул. 14-я линия, 63; e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it., ORCID ID: https://orcid.org/0000-0003-2943-7655
Котиева Инга Мовлиевна – доктор медицинских наук, ФГБУ «Национальный медицинский исследовательский центр онкологии» МЗ РФ. 344037, Россия, г. Ростов-на-Дону, ул. 14-я линия, 63; e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it., ORCID ID: https://orcid.org/0000-0003-0252-4708
Морозова Мария Игоревна – врач, ФГБУ «Национальный медицинский исследовательский центр онкологии» МЗ РФ. 344037, Россия, г. Ростов-на-Дону, ул. 14-я линия, 63; e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it., ORCID ID: https://orcid.org/0000-0001-7640-6021
Образец цитирования
Франциянц Е.М., Бандовкина В.А., Каплиева И.В., Сурикова Е.И., Нескубина И.В., Трепитаки Л.К., Черярина Н.Д., Погорелова Ю.А., Немашкалова Л.А., Шихлярова А.И., Котиева И.М., Морозова М.И. Влияние сахарного диабета на уровень факторов роста в карциноме Герена у крыс обоего пола. Ульяновский медико-биологический журнал. 2021; 3: 129–140. DOI: 10.34014/2227-1848-2021-3-129-140.