urovestВестник урологииUrology Herald2308-6424Rostov State Medical University10.21886/2308-6424-2022-10-4-98-108urovest-629Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИORIGINAL ARTICLESВлияние таксанов на экспрессию miR-106 и miR-200с клетками рака предстательной железы in vivo и in vitroEffect of taxanes on the miR-106 and miR-200c expression in prostate cancer cells in vivo and in vitrohttps://orcid.org/0000-0002-5657-130XПлевакоД. С.PlevakoD. S.

Плевако Даниил Сергеевич — аспирант, лаборант-исследователь научной лаборатории субклеточных технологий НМИЦ онкологии имени Н.Н. Петрова Минздрава России.

197758, Санкт-Петербург, пос. Песочный, ул. Ленинградская, д. 68

Daniil S. Plevako — Postgrad. Student, Research Laboratory Assistant, Laboratory of Subcellular Technologies, Petrov National Medical Research Center of Oncology.

68 Leningradskaya St., Pesochniy, St.Petersburg 197758

plevako.daniil@yandex.ruhttps://orcid.org/0000-0002-2079-5061КнязеваМ. С.KnyazevaM. S.

Князева Маргарита Сергеевна — младший научный сотрудник научной лаборатории субклеточных технологий НМИЦ онкологии имени Н.Н. Петрова Минздрава России.

197758, Санкт-Петербург, пос. Песочный, ул. Ленинградская, д. 68

Margarita S. Knyazeva — Junior Researcher, Laboratory of Subcellular Technologies, Petrov National Medical Research Center of Oncology.

68 Leningradskaya St., Pesochniy, St.Petersburg 197758

margo9793@gmail.comhttps://orcid.org/0000-0003-4174-2839СидинаЕ. И.SidinaE. I.

Сидина Елена Игоревна — младший научный сотрудник научной лаборатории субклеточных технологий с группой онкоэндокринологии НМИЦ онкологии имени Н.Н. Петрова Минздрава России.

197758, Санкт-Петербург, пос. Песочный, ул. Ленинградская, д. 68

Elena I. Sidina — Junior Researcher, Laboratory of Subcellular Technologies with the Endocrine Oncology Unit, Petrov National Medical Research Center of Oncology.

68 Leningradskaya St., Pesochniy, St.Petersburg 197758

sidina@mail.ruhttps://orcid.org/0000-0002-6276-1716БеркутМ. В.BerkutM. V.

Беркут Мария Владимировна — кандидат медицинских наук, врач отделения онкоурологии НМИЦ онкологии им. Н.Н. Петрова Минздрава России.

197758, Санкт-Петербург, пос. Песочный, ул. Ленинградская, д. 68

Maria V. Berkut — M.D., Cand.Sc.(Med), Urologist, Oncological Urology Division, Petrov National Medical Research Institute of Oncology.

68 Leningradskaya St., Pesochniy, St.Petersburg 197758

berkutv91@gmail.comhttps://orcid.org/0000-0001-5183-5153РеваС. А.RevaS. A.

Рева Сергей Александрович — кандидат медицинских наук, научный сотрудник НМИЦ онкологии им. Н.Н. Петрова Минздрава России; заведующий онкологическим отделением №6 (андрологии и онкоурологии) НИЦ урологии ПСПбГМУ им. акад. И.П. Павлова Минздрава России.

197758, Санкт-Петербург, пос. Песочный, ул. Ленинградская, д. 68

Sergey A. Reva — M.D., Cand.Sc.(Med), Researcher, Petrov National Medical Research Center of Oncology; Head, Oncology Division No. 6 (Andrology and Oncological Urology), Research Center of Urology, Pavlov First Saint-Petersburg State Medical University (Pavlov University).

68 Leningradskaya St., Pesochniy, St.Petersburg 197758

sgreva79@mail.ruhttps://orcid.org/0000-0002-6542-2074ТолмачевС. С.TolmachevS. S.

Толмачев Станислав Сергеевич — врач патологоанатомического отделения НМИЦ онкологии имени Н.Н. Петрова Минздрава России.

197758, Санкт-Петербург, пос. Песочный, ул. Ленинградская, д. 68

Stanislav S. Tolmachev — M.D., Pathologist, Pathology Division, Petrov National Medical Research Center of Oncology.

68 Leningradskaya St., Pesochniy, St.Petersburg 197758

stas@tolmachyov.mehttps://orcid.org/0000-0002-2948-397XАртемьеваА. С.ArtemyevaA. S.

Артемьева Анна Сергеевна — кандидат медицинских наук, руководитель научной лаборатории морфологии опухолей НМИЦ онкологии имени Н.Н. Петрова Минздрава России.

197758, Санкт-Петербург, пос. Песочный, ул. Ленинградская, д. 68

Anna S. Artemyeva — M.D., Cand.Sc.(Med), Head, Research Laboratory of Tumor Morphology, Petrov National Medical Research Center of Oncology.

68 Leningradskaya St., Pesochniy, St.Petersburg 197758

oinochoya@mail.ruhttps://orcid.org/0000-0003-3850-7109НосовА. К.NosovA. K.

Носов Александр Константинович — кандидат медицинских наук, заведующий отделением онкоурологии, старший научный сотрудник отделения общей онкологии и урологии, доцент методического аккредитационно-симуляционного центра НМИЦ онкологии им. Н.Н. Петрова Минздрава России.

197758, Санкт-Петербург, пос. Песочный, ул. Ленинградская, д. 68

Aleksander K. Nosov — M.D., Cand.Sc.(Med), Head, Oncological Urology Division, Senior Researcher, Dept. of General Oncology and Urology, Assoc.Prof., Methodological Accreditation and Simulation Centre, Petrov National Medical Research Institute of Oncology.

68 Leningradskaya St., Pesochniy, St.Petersburg 197758

naku-ro@yandex.ruhttps://orcid.org/0000-0001-5334-7292МалекА. В.MalekA. V.

Малек Анастасия Валерьевна — доктор медицинских наук, заведующая научной лабораторией субклеточных технологий НМИЦ онкологии имени Н.Н. Петрова Минздрава России.

197758, Санкт-Петербург, пос. Песочный, ул. Ленинградская, д. 68

Anastasia V. Malek — M.D., Dr.Sc.(Med), Head, Laboratory of Subcellular Technologies with Endocrine Oncology Unit, Petrov National Medical Research Center of Oncology.

68 Leningradskaya St., Pesochniy, St.Petersburg 197758

anastasia@malek.com.ruНациональный медицинский исследовательский центр онкологии имени Н.Н. Петрова Минздрава РоссииРоссияPetrov National Medical Research Center of OncologyRussian Federation20222612202210498108Copyright © Плевако Д.С., Князева М.С., Сидина Е.И., Беркут М.В., Рева С.А., Толмачев С.С., Артемьева А.С., Носов А.К., Малек А.В., 20232023Плевако Д.С., Князева М.С., Сидина Е.И., Беркут М.В., Рева С.А., Толмачев С.С., Артемьева А.С., Носов А.К., Малек А.В.Plevako D.S., Knyazeva M.S., Sidina E.I., Berkut M.V., Reva S.A., Tolmachev S.S., Artemyeva A.S., Nosov A.K., Malek A.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.urovest.ru/jour/article/view/629Введение

Введение. Сочетание антиандрогенных и цитостатических препаратов в рамках нео-адьювантной терапии пациентов с локально-распространённым раком предстательной железы высокого риска (РПЖ-ВР) оправдано результатами ряда клинических испытаний. Но клинический эффект такой терапии в каждом случае определяется чувствительностью клеток опухоли к используемым препаратам, что определяет возможность разработки и применения технологий персонализации. МикроРНК — класс регуляторных молекул, изменения экспрессии которых в клетках РПЖ могут быть ассоциированы с чувствительностью / резистентностью опухоли к определённым цитостатикам, например, таксанам.

Цель исследования

Цель исследования. Идентифицировать потенциальные микроРНК-маркеры чувствительности клеток рака предстательной железы к таксаном.

Материалы и методы

Материалы и методы. Объектом для исследования служили образцы ткани РПЖ-ВР (n = 56), полученные после проведения радикальной простатэктомии, линии клеток РПЖ (PC-3, DU-145, LNCap). Выделение тотальной РНК проведено с помощью наборов miRNeasy FFPE Kit, LRU-100-50. Для полуколичественного анализа потенциально маркерных молекул микроРНК с помощью последовательных реакций обратной транскрипции ПЦР были использованы наборы реагентов miRCURY LNA miRNA Focus PCR Panel, All-MIR.

Результаты

Результаты. Воздействие таксанов на клетки РПЖ ассоциировано с активацией экспрессии miR-106b и снижением экспрессии miR-200c в условиях in vivo и in vitro.

Заключение

Заключение. Микро-РНК miR-106b и miR-200c участвуют в реакции клеток РПЖ на воздействие таксанов, поэтому терапевтическая модификация состава этих молекул в клетках РПЖ является потенциальной стратегией повышения чувствительности клеток к таксан-содержащей терапии. Соответствующая инновационная технология может быть востребована в рамках терапии пациентов с РПЖ-ВР.

Introduction

Introduction. A combination of antiandrogen and cytostatic drugs was justified in the neoadjuvant therapy of patients with high-risk prostate cancer (HiRPCa) in some clinical trials. The effectiveness of such therapy in each individual case depends on the sensitivity of cancer cells to the applied drugs. It makes possible the development of the new technologies to personalize therapeutic approach. MicroRNAs (miRNAs) are a class of regulatory molecules whose expression is altered in PCa cells and can be associated with the sensitivity/resistance of cancer cells to specific cytostatics, for instance, taxanes.

Objective

Objective. To identify the potential-marker miRNAs of PCa cells sensitivity to taxanes.

Materials and methods

Materials and methods. Samples of PCa tissue (n. 56) obtained from patients underwent neo-adjuvant therapy (antiandrogen and taxanes) and radical prostatectomy; PCa cell lines (PC-3, DU-145, LNCap). Total RNAs isolation was carried out using miRNeasy FFPE Kit, LRU-100-50; miRCURY LNA miRNA Focus PCR Panel, All-MIR kits were used for semi-quantitative analysis of potentially marker microRNA molecules using sequential reverse transcription and PCR.

Results

Results. The effect of taxanes on PCa cells is associated with up-regulation of miR-106b expression and down-regulation of miR-200c expression in both in vivo and in vitro conditions.

Conclusion

Conclusion. MiR-106b and miR-200c miRNAs are involved in the response of PCa cells to taxanes, and therapeutic modification of these molecules in PCa cells may present a potential strategy to increase their sensitivity to taxane-containing therapy. Appropriate innovative technology may be in demand in the treatment of HiRPCa-patients.

рак предстательной железымикроРНКтаксаныдоцетакселпаклитакселprostate cancermicroRNAtaxanesdocetaxelpaclitaxelИсследование выполнено в рамках государственного задания «Разработка и клиническая апробация методов диагностики и прогнозирования эффекта терапии онкологических заболеваний на основе анализа микроРНК в биопсийном материале» (№ 121032300206-4) 2021 – 2023.The study was funded within the framework of a state assignment by the Ministry of Healthcare of the Russian Federation «Development and clinical testing of methods for diagnosing and predicting the effect of cancer therapy based on microRNA analysis in biopsy material» (No. 121032300206-4) 2021-2023.ReferencesЗлокачественные новообразования в России в 2020 году (заболеваемость и смертность). Под ред. Каприна А.Д., Старинского В.В., Шохзадова А.О. Москва: МНИОИ им. П.А. Герцена − филиал ФГБУ «НМИЦ радиологии» Минздрава России; 2021. ISBN 978-5-85502-268-1. 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The authors declare that there are no conflicts of interest present.