外源性褪黑激素对B16小鼠实验性黑色素瘤的形态特征的影响

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详细

论证。持续长时间的光照会抑制松果腺的激素合成功能，导致褪黑激素水平降低，从而加速身体老化，增加与年龄相关的疾病发生频率，包括肿瘤，同时缩短寿命。褪黑激素具有明显的抗肿瘤作用，尤其是其抗增生作用更为突出。 黑色素瘤 — 人类最恶性的肿瘤之一，源于黑色素形成的细胞。 近年来，黑色素瘤患者中老年患者的比例不断增加，因此，可以将这种疾病归类为与年龄相关的疾病。有证据表明，褪黑激素缺乏和由此导致的身体昼夜节律结构紊乱是引发黑色素瘤的因素之一。

目的 — 外源性褪黑激素对B16小鼠实验性黑色素瘤的形态特征的影响

方法。这项研究在8周龄，体重为21～22克的BDF1(n = 60)杂种小鼠雄性中进行。所有动物都进行了皮下移植B16/F10黑色素瘤悬浮液。接下来，老鼠被分为两组，即对照组和实验组。对照组中的动物从研究的第一天起，胃内注射5毫克/公斤剂量的褪黑激素（Sigma，美国）。在肿瘤转染后的第15天，切除了肿瘤本身，以及肺部和肝脏。对肿瘤进行了病理形态学检查，确定了肺部和肝脏存在的转移。在苏木精和伊红染色的肿瘤组织切片上测量坏死面积，并通过测量细胞核横截面积和细胞横截面积计算肿瘤细胞中的核质比。使用GraphPad Prism v8.41（美国）软件进行了结果的构图和统计处理。

结果。已确认，注射褪黑激素可降低黑色素瘤小鼠在研究期间的死亡率，减少肿瘤转移的频率及其大小。此外，在实验组小鼠的黑色素瘤中，可以看到以病灶的萎缩和替代性变化形式出现的肿瘤消退迹象，以及肿瘤坏死面积在统计学上的显著增加。

结论。本研究表明，外源性褪黑激素对B16小鼠实验性黑色素瘤具有明显的抗肿瘤效果。所获得的结果可以更详细的规划多学科研究，用于深入探究褪黑激素的抗肿瘤作用机制。

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作者简介

David A. Areshidze

Petrovsky National Research Centre of Surgery

编辑信件的主要联系方式.
Email: labcelpat@mail.ru
ORCID iD: 0000-0003-3006-6281
SPIN 代码: 4348-6781

Cand. Sci. (Biology)

俄罗斯联邦, Moscow

Maxim V. Mnikhovich

Petrovsky National Research Centre of Surgery

Email: mnichmaxim@yandex.ru
ORCID iD: 0000-0001-7147-7912
SPIN 代码: 6975-6677

Cand. Sci. (Medicine)

俄罗斯联邦, Moscow

Roman V. Deev

Petrovsky National Research Centre of Surgery

Email: romdey@gmail.com
ORCID iD: 0000-0001-8389-3841
SPIN 代码: 2957-1687

Cand. Sci. (Medicine), Associate Professor

俄罗斯联邦, Moscow

Maria A. Kozlova

Petrovsky National Research Centre of Surgery

Email: ma.kozlova2021@outlook.com
ORCID iD: 0000-0001-6251-2560
SPIN 代码: 5647-1372

Cand. Sci. (Biology)

俄罗斯联邦, Moscow

Anna I. Anurkina

Petrovsky National Research Centre of Surgery

Email: anyaaai1925@gmail.com
ORCID iD: 0009-0003-0011-1114
SPIN 代码: 9812-3412
俄罗斯联邦, Moscow

Denis V. Mishchenko

Federal Research Center of Problems of Chemical Physics and Medicinal Chemistry of the Russian Academy of Sciences

Email: mdv@icp.ac.ru
ORCID iD: 0000-0003-3779-3211
SPIN 代码: 4213-3318

Cand. Sci. (Biology)

俄罗斯联邦, Chernogolovka

Tatyana Е. Sashenkova

Federal Research Center of Problems of Chemical Physics and Medicinal Chemistry of the Russian Academy of Sciences

Email: tsashen52@mail.ru
ORCID iD: 0000-0002-2753-979X
俄罗斯联邦, Chernogolovka

Anton N. Turchin

Mechnikov North-Western State Medical University

Email: ktogrb@yandex.ru
ORCID iD: 0009-0008-5302-5769
俄罗斯联邦, Saint Petersburg

参考

  1. Anisimov VN. Light pollution, reproductive function and cancer risk. Neuro Endocrinol Lett. 2006;27(1–2):35–52.
  2. Straif K, Baan R, Grosse Y, et al. Carcinogenicity of shift-work, painting, and fire-fighting. Lancet Oncol. 2007;8(12):1065–1066. doi: 10.1016/S1470-2045(07)70373-X
  3. Pauley SM. Lighting for the human circadian clock: recent research indicates that lighting has become a public health issue. Med Hypotheses. 2004;63(4):588–596. doi: 10.1016/j.mehy.2004.03.020
  4. Stevens RG. Light-at-night, circadian disruption and breast cancer: assessment of existing evidence. Int J Epidemiol. 2009;38(4):963–970. doi: 10.1093/ije/dyp178
  5. Arushanian EB, Naumov SS. A wide range of pharmacological properties of melatonin. Reviews on Clinical Pharmacology and Drug Therapy. 2021;19(1):103–106. (In Russ.) doi: 10.17816/RCF191103-106 EDN: XKUIWB
  6. Sato K, Meng F, Francis H, et al. Melatonin and circadian rhythms in liver diseases: functional roles and potential therapies. J Pineal Res. 2020;68(3):e12639. doi: 10.1111/jpi.12639
  7. Zuev VA, Trifonov NI, Linkova NS, Kvetnaia TV. Melatonin as a molecular marker of age-related pathologies. Advances in Gerontology. 2017;30(1):62–69. (In Russ.) EDN: YHTMRF
  8. Anisimov VN, Vinogradova IA. Light regime, biorythms and organism aging. Aesthetic Medicine Bulletin. 2011;10(1):42–51. (In Russ.) EDN: OEVILV
  9. Anisimov VN. Light, aging, and cancer. Priroda. 2018;(6):19–22. (In Russ.) EDN: XQNOMP
  10. Kvetnaia TV, Polyakova VO, Proshaev KI, et al. Melatonin as a marker of ageing and age-associated diseases. RUDN Journal of Medicine. 2012;(S7):125–126. (In Russ.) EDN: RCADUR
  11. Slominski RM, Reiter RJ, Schlabritz-Loutsevitch N, et al. Melatonin membrane receptors in peripheral tissues: distribution and functions. Mol Cell Endocrinol. 2012;351(2):152–166. doi: 10.1016/j.mce.2012.01.004
  12. Pandi-Perumal SR, Trakht I, Srinivasan V, et al. Physiological effects of melatonin: Role of melatonin receptors and signal transduction pathways. Prog Neurobiol. 2008;85(3):335–353. doi: 10.1016/j.pneurobio.2008.04.001
  13. Malishevskaya NP, Sokolova AV, Demidov LV. The incidence of skin melanoma in the Russian Federation and federal districts. Medical Council. 2018;(10):161–165. (In Russ.) doi: 10.21518/2079-701X-2018-10-161-165 EDN: UUDAMY
  14. Garbe C, Peris K, Hauschild A, et al. Diagnosis and treatment of melanoma: European consensus-based interdisciplinary guideline. Eur J Cancer. 2010;46(2):270–283. doi: 10.1016/j.ejca.2009.10.032
  15. Erkenova FD, Puzin SN. Statistics of melanoma in Russia and Europe. Medical and Social Expert Evaluation and Rehabilitation. 2020;23(1):44–52. (In Russ.) doi: 10.17816/MSER34259 EDN: WIAAEF
  16. de Assis LVM, Moraes MN, Mendes D, et al. Loss of Melanopsin (OPN4) leads to a Faster cell cycle progression and growth in murine melanocytes. Curr Issues Mol Biol. 2021;43(3):1436-1450. doi: 10.3390/cimb43030101
  17. Lubov JE, Cvammen W, Kemp MG. The impact of the circadian clock on skin physiology and cancer development. Int J Mol Sci. 2021;22(11):6112. doi: 10.3390/ijms22116112
  18. Mubashshir M, Ahmad N, Sköld HN, Ovais M. An exclusive review of melatonin effects on mammalian melanocytes and melanoma. Exp Dermatol. 2023;32(4):324–330. doi: 10.1111/exd.14715
  19. Jansen R, Osterwalder U, Wang SQ, et al. Photoprotection: part II. Sunscreen: development, efficacy, and controversies. J Am Acad Dermatol. 2013;69(6):867.e1–14. doi: 10.1016/j.jaad.2013.08.022
  20. Slominski AT, Hardeland R, Zmijewski MA, et al. Melatonin: a cutaneous perspective on its production, metabolism, and functions. J Invest Dermatol. 2018;138(3):490–499. doi: 10.1016/j.jid.2017.10.025
  21. Acuña-Castroviejo D, Escames G, Venegas C, et al. Extrapineal melatonin: sources, regulation, and potential functions. Cell Mol Life Sci. 2014;71(16):2997–3025. doi: 10.1007/s00018-014-1579-2
  22. Alvarez-Artime A, Cernuda-Cernuda R, Francisco-Artime-Naveda, et al. Melatonin-induced cytoskeleton reorganization leads to inhibition of melanoma cancer cell proliferation. Int J Mol Sci 2020;21(2):548. doi: 10.3390/ijms21020548
  23. Cutando A, López-Valverde A, Arias-Santiago S, et al. Role of melatonin in cancer treatment. Anticancer Res. 2012;32(7):2747–2753.
  24. Treshchalina EM, Zhukova OS, Gerasimova GK, et al. Methodological recommendations for the preclinical study of the antitumor activity of drugs. In: Guidelines for conducting preclinical studies of drugs. Pt. 1. Moscow: Grif i K; 2012. P:640–656. (In Russ.)
  25. Broeke J, Pérez JMM, Pascau J. Image Processing with ImageJ. Birmingham: Packt Publishing; 2015.
  26. Franco PIR, do Carmo Neto JR, Milhomem AC, et al. Antitumor effect of melatonin on breast cancer in experimental models: a systematic review. Biochim Biophys Acta Rev Cancer. 2023;1878(1):188838. doi: 10.1016/j.bbcan.2022.188838
  27. Fathizadeh H, Mirzaei H, Asemi Z. Melatonin: an anti-tumor agent for osteosarcoma. Cancer Cell Int. 2019;19:319. doi: 10.1186/s12935-019-1044-2
  28. Shen D, Ju L, Zhou F, et al. The inhibitory effect of melatonin on human prostate cancer. Cell Commun Signal. 2021;19(1):34. doi: 10.1186/s12964-021-00723-0
  29. Su SC, Hsieh MJ, Yang WE, et al. Cancer metastasis: mechanisms of inhibition by melatonin. J Pineal Res. 2017;62(1). doi: 10.1111/jpi.12370
  30. Martínez-Campa C, Álvarez-García V, Alonso-González C, et al. Melatonin and its role in the epithelial-to-mesenchymal transition (EMT) in cancer. Cancers (Basel). 2024;16(5):956. doi: 10.3390/cancers16050956
  31. Lu KH, Lin CW, Hsieh YH, et al. New insights into antimetastatic signaling pathways of melatonin in skeletomuscular sarcoma of childhood and adolescence. Cancer Metastasis Rev. 2020;39(1):303–320. doi: 10.1007/s10555-020-09845-2
  32. Wang L, Wang C, Choi WS. Use of melatonin in cancer treatment: where are we? Int J Mol Sci. 2022;23(7):3779. doi: 10.3390/ijms23073779
  33. Blask DE, Dauchy RT, Sauer LA, Krause JA. Melatonin uptake and growth prevention in rat hepatoma 7288CTC in response to dietary melatonin: melatonin receptor-mediated inhibition of tumor linoleic acid metabolism to the growth signaling molecule 13-hydroxyoctadecadienoic acid and the potential role of phytomelatonin. Carcinogenesis. 2004;25(6):951–960. doi: 10.1093/carcin/bgh090
  34. Laothong U, Pinlaor P, Hiraku Y, et al. Protective effect of melatonin against Opisthorchis viverrini-induced oxidative and nitrosative DNA damage and liver injury in hamsters. J Pineal Res. 2010;49(3):271–282. doi: 10.1111/j.1600-079X.2010.00792.x

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2. Fig. 2. Melanoma in mice of the control group: a, subcutaneous tumor node of epithelioid cell melanoma; b, areas of muscle infiltration with tumor cells in the projection of the tumor growth zone, necrosis with an area of leukocytic infiltration (black arrow), vascular wall with focal necrosis and focal lymphoplasmacytic infiltration (white arrow); c, a cell in the state of apoptosis in the thickness of the regressive part of the tumor (white arrow), focal perivascular infiltrate (black arrow). Hematoxylin and eosin staining, 200x magnification.

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3. Fig. 3. Melanoma in mice of the experimental group: a, focus of necrosis (black arrow) surrounded by inflammatory cell cluster and interstitial edema (white arrow); b, regressive part of the tumor with dystrophic changes in tumor cells (black arrow), prominent lymphoplasmacytic infiltration and extensive zone of necrosis (white arrow); c, necrosis (black arrow) and apoptotic bodies in the tumor. Hematoxylin and eosin staining; magnification: a, b, 100x; c, 200x.

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4. Fig. 4. Morphometric parameters of B16 melanoma cells in mice: a, nucleus cross-sectional area (μm2); b, cell cross-sectional area (μm2); c, nuclear-cytoplasmic ratio; **, p ≤ 0.005, ***, p ≤ 0.0005 when comparing two groups.

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