Preview

Research and Practical Medicine Journal

Advanced search

The impact of diabetes mellitus on levels of sex hormones and their receptors in tumor tissues in female rats with Guerin’s carcinoma

https://doi.org/10.17709/2410-1893-2022-9-1-2

Abstract

Purpose of the study. Analysis of the effect of DM on levels of sex hormones and their receptors in tumor and perifocal tissues in outbred white female rats.

Materials and methods. Outbred white female rats were divided into 2 groups, 18 rats each: control group – with transplantable Guerin’s carcinoma, main group – with transplantable Guerin’s carcinoma growing in presence of DM. DM was reproduces in animals by the single intraperitoneal alloxan injection (150 mg/kg body weight). Animals were killed after 10 days of the tumor growth. Levels of hormones (estradiol, testosterone, progesterone and prolactin) and their receptors (RЕα, RЕβ, RA and RP4) were measured by ELISA in tumor and perifocal tissues in animals of the control and main groups.

Results. Female rats with Guerin’s carcinoma growing in presence of DM showed an increase in glucose in tumor and perifocal tissues by 1.8 times (р < 0.05) and 7.6 times, respectively, compared to the levels in the control group. Levels of E2 were increased, respectively, by 2.4 and 9.5 times; P4 – by 2.1 and 3.0 times; PRL – by 2.7 and 4.4 times. T was increased in perifocal tissues by 2.2 times and was unchanged in tumor tissues. RЕα and RP4 were elevated by 3.9 and 3.0 times, respectively, only in tumor tissues, and RA by 3.9 times only in perifocal tissues. The REα/RЕβ ratio was increased only in the tumor by 3.2 times. The Е2/RЕβ ratio was increased in tumor and perifocal tissues by 2.0 and 9.6 times, respectively. The T/RA ratio was decreased in the tumor and its perifocal area by 1.4 (р < 0.05) and 2.0 times, respectively. The opposite changes were observed in the Е2/RЕα and P4/RP4 ratios: a decrease in the tumor by 1.6 and 1.4 times, respectively (р < 0.05), and an increase in the perifocal area by 9.8 and 2.5 times, respectively.

Conclusion. Female rats with Guerin’s carcinoma growing in presence of DM demonstrated local hyperglycemia, changes in the levels of sex steroids and a misbalance in their receptors in tumor and perifocal tissues causing active metastasis and reduced average survival of animals.

 

About the Authors

E. M. Frantsiyants
National Medical Research Centre for Oncology
Russian Federation

Elena M. Frantsiyants – Dr. Sci. (Biol.), professor, Deputy General Director for Science, SPIN: 9427-9928, AuthorID: 462868, ResearcherID: Y-1491-2018, Scopus Author ID: 55890047700

63 14 line str., Rostov-on-Don 344037, Russian Federation



V. A. Bandovkina
National Medical Research Centre for Oncology
Russian Federation

Valeriya A. Bandovkina – Dr. Sci. (Biol.), senior researcher of the laboratory for the study of pathogenesis of malignant tumors, SPIN: 8806-2641, AuthorID: 696989, ResearcherID: AAG-8708-2019, Scopus Author ID: 57194276288

63 14 line str., Rostov-on-Don 344037, Russian Federation



I. V. Kaplieva
National Medical Research Centre for Oncology
Russian Federation

Irina V. Kaplieva – Dr. Sci. (Med.), senior researcher of the laboratory for the study of pathogenesis of malignant tumors, SPIN: 5047-1541, AuthorID: 734116

63 14 line str., Rostov-on-Don 344037, Russian Federation



E. I. Surikova
National Medical Research Centre for Oncology
Russian Federation

Ekaterina I. Surikova – Cand. Sci. (Biol.), senior research fellow at the Laboratory for the study of the pathogenesis of malignant tumors, SPIN: 2401-4115, AuthorID: 301537, ResearcherID: AAG-8748-2019, Scopus Author ID: 6507092816

63 14 line str., Rostov-on-Don 344037, Russian Federation



Yu. A. Pogorelova
National Medical Research Centre for Oncology
Russian Federation

Yulia A. Pogorelova – Cand. Sci. (Biol.), senior research fellow at Laboratory of Malignant Tumor Pathogenesis Study, SPIN: 2168-8737, AuthorID: 558241, Scopus Author ID: 37026863400

63 14 line str., Rostov-on-Don 344037, Russian Federation



N. D. Cheryarina
National Medical Research Centre for Oncology
Russian Federation

Natalia D. Cheryarina – laboratory assistant at the laboratory for the study of the pathogenesis of malignant tumors, SPIN: 2189-3404, AuthorID: 558243

63 14 line str., Rostov-on-Don 344037, Russian Federation



I. M. Kotieva
National Medical Research Centre for Oncology
Russian Federation

Inga M. Kotieva – Dr. Sci. (Med.), senior research fellow, Laboratory of Study of Malignant Tumor Pathogenesis, SPIN: 3478-5811, AuthorID: 637665

63 14 line str., Rostov-on-Don 344037, Russian Federation



M. I. Morozova
National Medical Research Centre for Oncology
Russian Federation

Maria I. Morozova – pediatrician, SPIN: 6030-8108, AuthorID: 1116725

63 14 line str., Rostov-on-Don 344037, Russian Federation



A. I. Shikhlyarova
National Medical Research Centre for Oncology
Russian Federation

Alla I. Shikhlyarova – Dr. Sci. (Biol.), Professor, senior researcher, Laboratory of Study of Malignant Tumor Pathogenesis, SPIN: 6271-0717, AuthorID: 482103, Scopus Author ID: 6507723229

63 14 line str., Rostov-on-Don 344037, Russian Federation



References

1. Wu T, Yang F, Chan WWL, Lam CLK, Wong CKH. Healthcare utilization and direct medical cost in the years during and after cancer diagnosis in patients with type 2 diabetes mellitus. J Diabetes Investig. 2020 Nov;11(6):1661–1672. https://doi.org/10.1111/jdi.13308

2. Park Y, Colditz GA. Diabetes and adiposity: a heavy load for cancer. Lancet Diabetes Endocrinol. 2018 Feb;6(2):82–83. https://doi.org/10.1016/S2213-8587(17)30396-0

3. Shlomai G, Neel B, LeRoith D, Gallagher EJ. Type 2 Diabetes Mellitus and Cancer: The Role of Pharmacotherapy. J Clin Oncol. 2016 Dec 10;34(35):4261–4269. https://doi.org/10.1200/JCO.2016.67.4044

4. Noto H, Tsujimoto T, Noda M. Significantly increased risk of cancer in diabetes mellitus patients: A meta-analysis of epidemiological evidence in Asians and non-Asians. J Diabetes Investig. 2012 Feb 20;3(1):24–33. https://doi.org/10.1111/j.2040-1124.2011.00183.x

5. Ganguly S, Naik D, Muskara A, Mian OY. The Nexus of Endocrine Signaling and Cancer: How Steroid Hormones Influence Genomic Stability. Endocrinology. 2021 Jan 1;162(1):bqaa177. https://doi.org/10.1210/endocr/bqaa177

6. Yen PM. Classical nuclear hormone receptor activity as a mediator of complex biological responses: a look at health and disease. Best Pract Res Clin Endocrinol Metab. 2015 Aug;29(4):517–528. https://doi.org/10.1016/j.beem.2015.07.005

7. Sastre-Serra J, Valle A, Company MM, Garau I, Oliver J, Roca P. Estrogen down-regulates uncoupling proteins and increases oxidative stress in breast cancer. Free Radic Biol Med. 2010 Feb 15;48(4):506–512. https://doi.org/10.1016/j.freeradbiomed.2009.11.025

8. Haffner MC, Aryee MJ, Toubaji A, Esopi DM, Albadine R, Gurel B, et al. Androgen-induced TOP2B-mediated double-strand breaks and prostate cancer gene rearrangements. Nat Genet. 2010 Aug;42(8):668–675. https://doi.org/10.1038/ng.613

9. Nichol AM, Chan EK, Lucas S, Smith SL, Gondara L, Speers C, et al. The Use of Hormone Therapy Alone Versus Hormone Therapy and Radiation Therapy for Breast Cancer in Elderly Women: A Population-Based Study. Int J Radiat Oncol Biol Phys. 2017 Jul 15;98(4):829– 839. https://doi.org/10.1016/j.ijrobp.2017.02.094

10. Cagnacci A, Venier M. The Controversial History of Hormone Replacement Therapy. Medicina (Kaunas). 2019 Sep 18;55(9):E602. https://doi.org/10.3390/medicina55090602

11. Michmerhuizen AR, Chandler B, Olsen E, Wilder-Romans K, Moubadder L, Liu M, et al. Seviteronel, a Novel CYP17 Lyase Inhibitor and Androgen Receptor Antagonist, Radiosensitizes AR-Positive Triple Negative Breast Cancer Cells. Front Endocrinol (Lausanne). 2020;11:35. https://doi.org/10.3389/fendo.2020.00035

12. Patent No. 2375758 C1 Russian Federation. 10.12.2009. Application No. 2008133091/14 dated 11.08.2008. Sidorenko YuS, Franzyants EM, Komarova EF, Pogorelova YuA, Shikhlyarova AI. Method of obtaining experimental malignant lung tumors. (In Russ.).

13. Kit OI, Franciyanc EM, Kaplieva IV, Tripitaki LK, Evstratova OF. A method for reproduction of metastases in the liver. Bulletin of Experimental Biology and Medicine. 2014;157(6):745–747. (In Russ.).

14. Kit OI, Franciyanc EM, Dimitriadi SN, Shevchenko AN, Kaplieva IV, Tripitaki LK. Neoangiogenesis and fibrinolytic system biomarkers expression in the dynamics of experimental kidney ischemia in rats. Experimental and Clinical Urology. 2015;(1):20–23. (In Russ.).

15. Daniel AR, Hagan CR, Lange CA. Progesterone receptor action: defining a role in breast cancer. Expert Rev Endocrinol Metab. 2011 May 1;6(3):359–369. https://doi.org/10.1586/eem.11.25

16. Wang M, Yang Y, Liao Z. Diabetes and cancer: Epidemiological and biological links. World J Diabetes. 2020 Jun 15;11(6):227–238. https://doi.org/10.4239/wjd.v11.i6.227

17. Carnesecchi J, Malbouyres M, de Mets R, Balland M, Beauchef G, Vié K, et al. Estrogens induce rapid cytoskeleton re-organization in human dermal fibroblasts via the non-classical receptor GPR30. PLoS One. 2015;10(3):e0120672. https://doi.org/10.1371/journal.pone.0120672

18. Coricovac D, Dehelean C, Moaca E-A, Pinzaru I, Bratu T, Navolan D, et al. Cutaneous Melanoma-A Long Road from Experimental Models to Clinical Outcome: A Review. Int J Mol Sci. 2018 May 24;19(6):E1566. https://doi.org/10.3390/ijms19061566

19. Noto H. Unfolding link between diabetes and cancer. J Diabetes Investig. 2017 Aug 8;9(3):473–474. https://doi.org/10.1111/jdi.12725

20. Suh S, Kim KW. Diabetes and Cancer: Cancer Should Be Screened in Routine Diabetes Assessment. Diabetes Metab J. 2019 Dec;43(6):733–743. https://doi.org/10.4093/dmj.2019.0177

21. Barclay AW, Petocz P, McMillan-Price J, Flood VM, Prvan T, Mitchell P, et al. Glycemic index, glycemic load, and chronic disease risk–a meta-analysis of observational studies. Am J Clin Nutr. 2008 Mar;87(3):627–637. https://doi.org/10.1093/ajcn/87.3.627

22. Williamson TT, Ding B, Zhu X, Frisina RD. Hormone replacement therapy attenuates hearing loss: Mechanisms involving estrogen and the IGF-1 pathway. Aging Cell. 2019 Jun;18(3):e12939. https://doi.org/10.1111/acel.12939

23. Shepard BD. Sex differences in diabetes and kidney disease: mechanisms and consequences. Am J Physiol Renal Physiol. 2019 Aug 1;317(2):F456–F462. https://doi.org/10.1152/ajprenal.00249.2019

24. Hong J, Stubbins RE, Smith RR, Harvey AE, Núñez NP. Differential susceptibility to obesity between male, female and ovariectomized female mice. Nutr J. 2009 Feb 17;8:11. https://doi.org/10.1186/1475-2891-8-11

25. Renoir J-M, Marsaud V, Lazennec G. Estrogen receptor signaling as a target for novel breast cancer therapeutics. Biochem Pharmacol. 2013 Feb 15;85(4):449–465. https://doi.org/10.1016/j.bcp.2012.10.018

26. Arnal J-F, Lenfant F, Metivier R, Flouriot G, Henrion D, Adlanmerini M, et al. Membrane and Nuclear Estrogen Receptor Alpha Actions: From Tissue Specificity to Medical Implications. Physiol Rev. 2017 Jul 1;97(3):1045–1087. https://doi.org/10.1152/physrev.00024.2016

27. Verma A, Schwartz N, Cohen DJ, Patel V, Nageris B, Bachar G, et al. Loss of Estrogen Receptors is Associated with Increased Tumor Aggression in Laryngeal Squamous Cell Carcinoma. Sci Rep. 2020 Mar 6;10(1):4227. https://doi.org/10.1038/s41598-020-60675-2

28. Roma A, Spagnuolo PA. Estrogen Receptors Alpha and Beta in Acute Myeloid Leukemia. Cancers (Basel). 2020 Apr 8;12(4):E907. https://doi.org/10.3390/cancers12040907


Supplementary files

Review

For citations:


Frantsiyants E.M., Bandovkina V.A., Kaplieva I.V., Surikova E.I., Pogorelova Yu.A., Cheryarina N.D., Kotieva I.M., Morozova M.I., Shikhlyarova A.I. The impact of diabetes mellitus on levels of sex hormones and their receptors in tumor tissues in female rats with Guerin’s carcinoma. Research and Practical Medicine Journal. 2022;9(1):23-32. (In Russ.) https://doi.org/10.17709/2410-1893-2022-9-1-2

Views: 453


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 2410-1893 (Online)