Pathomorphological analysis of salinomycin and nanodiamonds efficacy on Lewis lung carcinoma in mice

Cover Page

Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access

Abstract

Relevance. The search for new antitumor drugs and their selective delivery directly to the tumor site is an important task of modern oncology. For these purposes, currently, the use of various nanoparticles as carriers of medicinal substances is of great importance. The pathomorphological features of tumor cells under the action of salinomycin and nanodiamonds have not been studied enough.

The aim of the work was to study the pathomorphological features of the tumor in mice with transplanted Lewis lung carcinoma, who were treated with the ionoform antibiotic salinomycin and a combination of salinomycin with nanodiamonds.

Material and methods. 20 mice were divided into 4 groups. 1 – control group; 2 – mice received salinomycin; 3 – salinomycin and nanodiamonds; 4 – nanodiamonds. A morphometric study of histological and immunohistochemical tumor preparations stained for PCNA was carried out.

Results. Salinomycin is established to have an antineoplastic action. The use of nanodiamonds did not significantly affect the morphofunctional characteristics of Lewis lung carcinoma and did not change the antitumor activity of salinomycin.

Conclusion. Salinomycin has an antitumor effect and requires further research.

Full Text

Restricted Access

About the authors

Viktor Vasilyevich Popuchiev

National Medical Research Radiological Сentre of the Ministry of Health of the Russian Federation

Author for correspondence.
Email: popuchiev@mrrc.obninsk.ru
ORCID iD: 0000-0001-9304-7323

A.F. Tsyb Medical Radiological Research Center, Doctor of Medical Sciences, Senior Researcher

Russian Federation, Koroleva str., 4, Obninsk, Kaluga Region, 249036

Elena Mikhailovna Yatsenko

National Medical Research Radiological Сentre of the Ministry of Health of the Russian Federation

Email: yatsenko@mrrc.obninsk.ru
ORCID iD: 0000-0003-0869-0133

A.F. Tsyb Medical Radiological Research Center, Senior Researcher, Candidate of Biological Sciences

Russian Federation, Koroleva str., 4, Obninsk, Kaluga Region, 249036

Natalia Konstantinovna Fomina

National Medical Research Radiological Сentre of the Ministry of Health of the Russian Federation

Email: nkfomina@rambler.ru
ORCID iD: 0000-0002-1499-1349

A.F. Tsyb Medical Radiological Research Center, Senior Researcher, Candidate of Biological Sciences

Russian Federation, Koroleva str., 4, Obninsk, Kaluga Region, 249036

Lyudmila Nikolaevna Mikhina

National Medical Research Radiological Сentre of the Ministry of Health of the Russian Federation

Email: mikhina1976@mail.ru
ORCID iD: 0000-0001-7600-7901

A.F. Tsyb Medical Radiological Research Center, Senior Researcher

Russian Federation, Koroleva str., 4, Obninsk, Kaluga Region, 249036

Leonid Petrovich Zhavoronkov

National Medical Research Radiological Сentre of the Ministry of Health of the Russian Federation

Email: leonid.petrovich@inbox.ru
ORCID iD: 0000-0001-5100-9118

A.F. Tsyb Medical Radiological Research Center, Doctor of Medical Sciences, Professor, Рrofessor of the Scientific and Educational Department

Russian Federation, Koroleva str., 4, Obninsk, Kaluga Region, 249036

Vadim Vasilyevich Yuzhakov

National Medical Research Radiological Сentre of the Ministry of Health of the Russian Federation

Email: ks.med@mail.ru
ORCID iD: 0000-0002-2854-6289

A.F. Tsyb Medical Radiological Research Center, Candidate of Medical Sciences, head of the Laboratory of Radiation Pathomorphology

Russian Federation, Koroleva str., 4, Obninsk, Kaluga Region, 249036

Anatoly Georgievich Konoplyannikov

National Medical Research Radiological Сentre of the Ministry of Health of the Russian Federation

Email: ks.med@mail.ru
ORCID iD: 0000-0003-2766-9030

A.F. Tsyb Medical Radiological Research Center, Doctor of Biological sciences, Professor, head of the Department of Cellular and Experimental Radiation Therapy

Russian Federation, Koroleva str., 4, Obninsk, Kaluga Region, 249036

References

  1. Gupta P.B., Onder Т.T., Jiang G., Tao K., Kuperwasser C., Weinberg R.A., Lander E.S. Identification of selective inhibitors of cancer stem cells by high-throughput screening. Cell. 2009; 138 (4): 645–59. doi: 10.1016/j.cell.2009.06.034
  2. Huczynski A. Salinomycin: a new cancer drug candidate. Chem. Biol. Drug. Des. 2012; 79 (3): 235–8. doi: 10.1111/j.1747-0285.2011.01287
  3. Zhang Y., Zhang H., Wang X., Wang J., Zhang X, Zhang Q. The eradication of breast cancer and cancer stem cells using octreotide modifed paclitaxel active targeting micelles and salinomycin passive targeting micelles. Biomaterials. 2012; 33 (2): 679–91. doi: 10.1016/j.biomaterials.2011.09.072
  4. Москалева Е.Ю., Северин С.Е. Противоопухолевая активность ионофорного антибиотика салиномицина: мишень – опухолевые стволовые клетки. Молекулярная медицина. 2012; 6: 28–37. doi: 10.29296/24999490-2018-02-02. [Moskaleva Е.Yu., Severin S.Е. Anti-tumor activity of the ionophore antibiotic salinomycin: the target – cancer stem cells. Molekulyarnaya meditsina. 2012; 6: 28–37. doi: 10.29296/24999490-2018-02-02 (in Russian)]
  5. Москалева Е. Ю. Кондрашева И.Г., Попова О.Н., Семочкина Ю.П., Шмаргун А.М., Северин С.Е. Цитотоксическая активность ионофорного антибиотика салиномицина и его комбинации с противоопухолевыми препаратами в отношении меланомы. Молекулярная медицина. 2013; 3: 56–61. [Moskaleva E.Yu., Kondrasheva I.G., Popova O.N., Semochkina Yu.P., Shmargun A.M., Severin S.E. Cytotoxic activity of the ionophore antibiotic salinomycin and its combination with anticancer preparations against human melanoma cells. Molekulyarnaya meditsina. 2013; 3: 56–61 (in Russian)]
  6. Корман Д.Б., Островская Л.А, Блюхтерова Н.В., Рыкова В.А., Фомина М.М. Наночастицы золота как потенциальные радиосенсибилизирующие и цитотоксические агенты. Биофизика. 2021; 66 (6): 1229–45. doi: 10.1134/0006350921060063. [Korman D.B., Ostrovskaya L.A, Blyuhterova N.V., Rykova V.A., Fomina M.M. Gold nanoparticles as potential radiosensitizing and cytotoxic agents. BIOPHYSICS. 2021; 66 (6): 1229–45. doi: 10.31857/000630292106020 (in Russian)]
  7. Пальмина Н.П., Сажина Н.Н., Богданова Н.Г., Антипова А.С., Мартиросова Е.И., Плащина И.Г., Каспаров В.В., Семёнова М.Г. Физико-химические свойства липосом, реконструированных из липидов печени и головного мозга мышей, принимавших нанолипосомальные комплексы. Биофизика. 2021; 66 (5): 925–36. doi: 10.31857/0006302921050100 [Palmina N.P., Sazhina N.N., Bogdanova N.G., Antipova A.S., Martirosova E.I., Plashchina I.G., Kasparov V.V., Semenova M.G. The physico-chemical properties of liposomes made from lipids of the liver and brain of mice receiving nanolipid complexes. BIOPHYSICS. 2021; 66 (5): 925–36 (in Russian)]
  8. Новикова О.Д., Набережных Г.А., Сергеев А.А. Наноструктурные биосенсоры на основе компонентов бактериальных мембран. Биофизика. 2021; 66 (4): 668–83 doi: 10.31857/0006302921040062 [Novikova O.D., Naberezhnykh G.A., Sergeev A.A. Nanostructured biosensors based on components of bacterial membranes. BIOPHYSICS. 2021; 66 (4): 668–83 (in Russian)]
  9. Коноплянников А.Г, Алексенский А. Е., Злотин С. Г., Смирнов Б. Б., Кальсина С.Ш., Лепехина Л. А., Семенкова И. В., Агаева Е. В., Бабоян С. Б., Рюмшина Е.А., Носаченко В. В., Коноплянников М. А. Комплексы детонационных наноалмазов с ингибиторами раковых стволовых клеток или паракринными продуктами мезенхимальных стволовых клеток как новые потенциальные лекарственные средства. Кристаллография. 2015; 60 (5): 831–6. doi: 10.7868/0023476115050045. [Konoplyannikov A.G, Aleksenskij A.E., Zlotin S.G., Smirnov B.B., Kal'sina S.Sh., Lepehina L.A., Semenkova I.V., Agaeva E.V., Baboyan S.B., Ryumshina E.A., Nosachenko V.V., Konoplyannikov M.A. Complexes of detonation nanodiamonds with cancer stem cell inhibitors or paracrine products of mesenchymal stem cells as new potential drugs. Crystallography. 2015; 60 (5): 831–6. doi: 10.7868/0023476115050045 (in Russian)]
  10. Петриев В.М., Тищенко В.К., Михайловская А.А., Коноплянников А.Г. Фармакокинетика наноалмазов, меченных 188 Re, в организме мышей с экспериментальной карциномой Эрлиха. Радиация и риск. 2017; 26 (2): 62–71. doi: 10.21870/0131-3878-2017-26-2-62-71. [Petriev V.M. Tishchenko V.K., Mikhailovskaya A.A., Konoplyannikov A.G. Pharmacokinetics of 188Re-nanodiamonds complex in mice bearing experimental Ehrlich carcinoma. Radiation & Risk. 2017; 26 (2): 62–71. doi: 10.21870/0131-3878-2017-26-2-62-71 (in Russian)]
  11. Коноплянников М.А., Тимошенко В.Ю., Каргина Ю.В., Юсубалиева Г.М., Кальсин В.А., Коноплянников А.Г., Баклаушев В.П., Тимашев П.С. Комплекс салиномицина с наночастицами кремния эффективно ингибирует опухолевый рост in vitro и in vivo. Гены и Клетки. 2019; 14 (3): 117. doi: 10.23868/gc122870. [Konoplyannikov M.A., Timoshenko V.Y., Kargina Y.V., Yusubalieva G.M., Kal'sin V.A., Konoplyannikov A.G., Baklaushev V.P., Timashev P.S. The complex of salinomycin with silicium nanoparticles effectively inhibits tumor growth in vitro and in vivo. Genes & Cells. 2019; 14 (3): 117. doi: 10.23868/gc122870 (in Russian)]

Supplementary files

Supplementary Files
Action
1. JATS XML
2. Fig. 1. Morphology of CLL in mice of the 1st control group: a – histological pattern of the tumor node on day 21 after implantation (scan), hematoxylin and eosin; b – zone of invasive growth of CLL (×200), hematoxylin and eosin; c – zone of solid structure of CLL (×400), hematoxylin and eosin; g – serial section of the CLL to Fig. 1a (scan), immune-stained with PCNA; d – proliferative activity of tumor cells in the growth zone of CLL (×200), PCNA

Download (237KB)
3. Fig. 2. Morphology of CLL in group 2 mice that were injected with salinomycin: a – histological picture of the tumor node (scan), stained with hematoxylin and eosin; b – the growth zone of CLL (×200), hematoxylin and eosin; c – zone of solid structure in the proximal part of CLL (×400), hematoxylin and eosin; d – serial section of CLL, immuno-stained with PCNA (scan); e – proliferative activity of tumor cells in the growth zone of CLL (×200), PCNA

Download (234KB)
4. Fig. 3. Morphology of CLL in group 3 mice, with the combined use of salinomycin and nanodiamonds: a – histological picture of the tumor node (scan), stained with hematoxylin and eosin; b – the growth zone of CLL (×200), hematoxylin and eosin; c – zone of solid structure in the proximal part of CLL (×400), hematoxylin and eosin; d – serial section of CLL, immuno-stained with PCNA (scan); e – immuno-staining of tumor cell nuclei on PCNA in the growth zone of CLL (×200), PCNA

Download (229KB)
5. Fig. 4. Morphology of CLL in group 4 mice treated with nanodiamonds: a – histological picture of the tumor node (scan), hematoxylin and eosin; b – vascularization of the CLL growth zone (×200), hematoxylin and eosin; c – zone of solid structure in the proximal part of CLL (×400), hematoxylin and eosin; d – serial section of CLL, immuno-stained with PCNA (scan); e – proliferative activity of tumor cells in the growth zone of CLL (×200), PCNA

Download (251KB)

Copyright (c) 2024 Russkiy Vrach Publishing House