ADİPONEKTİN’İN MCF-7 PROLİFERASYONU VE GİRELİN SEVİYESİ ÜZERİNE ETKİSİ

Year 2022, , 591 - 595, 27.12.2022

Uğur Şahin , Melda Şahin , Okan Sancer , Mustafa Calapoğlu , Nurgül Şenol

https://doi.org/10.17343/sdutfd.1177877

Abstract

Amaç
Lokal ve sistemik faktörlerin, östrojen reseptörü pozitif
meme kanseri riskinde artış olan postmenopozal
obez kadınlarda meme kanseri hücrelerinin büyümesini
yönlendirdiği gösterilmiştir. Postmenapozal
dönemdeki obez kadınlarda, dolaşımdaki girelin hormonunun
azaldığı, bazı tümör hücreleri tarafından
üretildiği ve ayrıca tümör büyümesini etkilediği gösterilmiştir.
Bu çalışmada, adiponektin uygulamasının
östrojen reseptörü pozitif MCF-7 meme kanseri hücre
hattındaki rolünü ve girelin seviyeleri üzerine olan etkilerini
araştırmayı amaçladık.
Gereç ve Yöntem
MCF-7 meme kanseri hücre hattı 2 boyutlu kültürde
çoğaltıldı. MCF-7 meme kanseri hücrelerine artan
konsantrasyonlarda adiponektin (50-5000 ng/mL) ile
muamele edilerek inhibisyon dozu belirlendi. MCF-7
meme kanseri hücre hattına 50, 100, 250 ve 500 ng/
mL konsantrasyonda adiponektin uygulanarak 24, 48
ve 72. Saatlerde örneklerde girelin seviyeleri enzim
bağlı immünosorbent analizi (ELISA) ile ölçüldü.
Bulgular
24, 48 ve 72. saate alınan MCF-7 meme kanseri hücre
hattı kültür örneklerinde 50, 100, 250 ve 500 ng/mL
adiponektin konsantrasyonuna bağlı olarak proliferasyonun
azaldığı bulundu. 24, 48 ve 72. saate alınan
MCF-7 meme kanseri hücre hattı kültür örneklerinde
50, 100, 250 ve 500 ng/mL adiponektin konsantrasyonuna
bağlı olarak girelin miktarında artış oluştuğu
bulundu.
Sonuç
Çalışmamızda MCF-7 meme kanseri hücre hattında
(ER/PR pozitif) anti-kanserojenik özelliği kanıtlanmış
olan ve aynı zamanda obezite ile negatif korelasyon
gösteren adiponektinin, girelin ile karşılıklı etkileşimlerinin,
ER pozitif meme kanserlerindeki rolünü ortaya
koymuş olduk.

Keywords

MCF-7, Adiponektin, Girelin, Hücre Kültürü, Meme Kanseri

Supporting Institution

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Project Number

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Thanks

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EFFECT OF ADIPONECTIN ON MCF-7 PROLIFERATION AND GHRELIN LEVEL

Abstract

Objective
Local and systemic factors have been shown to drive
the growth of breast cancer cells in postmenopausal
obese women who are at increased risk of
estrogen receptor-positive breast cancer. In obese
postmenopausal women, it has been shown that
circulating ghrelin hormone is decreased, produced
by some tumor cells, and also affects tumor growth.
In this study, we aimed to investigate the role of
adiponectin administration in estrogen receptor
positive MCF-7 breast cancer cell line and its effects
on ghrelin levels.
Material and Method
The MCF-7 breast cancer cell line was propagated
in 2D culture. The inhibition dose was determined by
treating MCF-7 breast cancer cells with increasing
concentrations of adiponectin (50-5000 ng/mL).
Ghrelin levels were measured at the 24th, 48th
,and 72nd hours by enzyme-linked immunosorbent
assay (ELISA) by administering adiponectin at a
concentration of 50, 100, 250 and 500 ng/mL to the
MCF-7 breast cancer cell line.
Results
In MCF-7 breast cancer cell line culture samples taken
at the 24th, 48th and 72nd hours, proliferation was
found to decrease depending on 50, 100, 250 and
500 ng/mL adiponectin concentration. It was found
that the amount of ghrelin increased depending on 50,
100, 250 and 500 ng/mL adiponectin concentration in
MCF-7 breast cancer cell line culture samples taken
at 24th, 48th and 72nd hours.
Conclusion
In our study, we revealed the role of adiponectin,
which has proven anti-carcinogenic properties in the
MCF-7 breast cancer cell line (ER/PR positive) and
also negatively correlated with obesity, and ghrelin, in
ER-positive breast cancers.

Keywords

Adiponectin, Ghrelin, Cell Culture, Breast Cancer, MCF-7

Project Number

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References

• 1. Özmen V, Özmen T, Doğru V. Breast Cancer in Turkey; An Analysis of 20.000 Patients with Breast Cancer. Eur J Breast Health. 2019 (3):141-146. doi: 10.5152/ejbh.2019.4890.
• 2. Dalamaga M, Diakopoulos KN, Mantzoros CS. The role of adiponectin in cancer: a review of current evidence. Endocrine reviews. 2012;33(4):547-94.
• 3. Zhao C, Wu M, Zeng N, Xiong M, Hu W, Lv W, et al. Cancer- associated adipocytes: Emerging supporters in breast cancer. Journal of Experimental & Clinical Cancer Research. 2020;39(1):1-17.
• 4. Sultana R, Kataki AC, Borthakur BB, et al. Imbalance in leptin- adiponectin levels and leptin receptor expression as chief contributors to triple negative breast cancer progression in Northeast India. Gene. 2017;621:51–8.
• 5. Chung SJ, Nagaraju GP, Nagalingam A, et al. ADIPOQ/adiponectin induces cytotoxic autophagy in breast cancer cells through STK11/LKB1-mediated activation of the AMPK-ULK1 axis. Autophagy. 2017;13(8):1386–403.
• 6. Wulster-Radcliffe MC, Ajuwon KM, Wang J, Christian JA, Spurlock ME. Adiponectin differentially regulates cytokines in porcine macrophages. Biochemical and biophysical research communications. 2004;316(3):924-9
• 7. Makris MC, Alexandrou A, Papatsoutsos EG, Malietzis G, Tsilimigras DI, Guerron AD, et al. Ghrelin and obesity: identifying gaps and dispelling myths. A reappraisal. in vivo. 2017;31(6):1047-50
• 8. Meier U, Gressner AM. Endocrine regulation of energy metabolism: review of pathobiochemical and clinical chemical aspects of leptin, ghrelin, adiponectin, and resistin. Clin Chem. 2004;50:1511–1525.
• 9. Sever S, White DL, Garcia JM. Is there an effect of ghrelin/ ghrelin analogs on cancer? A systematic review. Endocrine-related cancer. 2016;23(9):R393-R409
• 10. Russo F, Linsalata M, Clemente C, D’Attoma B, Orlando A, Campanella G, et al. The effects of fluorouracil, epirubicin, and cyclophosphamide (FEC60) on the intestinal barrier function and gut peptides in breast cancer patients: an observational study. BMC cancer. 2013;13(1):1-11
• 11. Nikander E, Tiitinen A, Laitinen K, Tikkanen M, Ylikorkala O. Effects of isolated isoflavonoids on lipids, lipoproteins, insulin sensitivity, and ghrelin in postmenopausal women. The Journal of Clinical Endocrinology & Metabolism. 2004;89(7):3567-72.
• 12. Au CC, Furness JB, Britt K, Oshchepkova S, Ladumor H, Soo KY, et al. Three-dimensional growth of breast cancer cells potentiates the anti-tumor effects of unacylated ghrelin and AZP- 531. Elife. 2020;9:e56913.
• 13. Ossus L, McKay JD, Canzian F, Wilkening S, Rinaldi S, Biessy C, et al. Polymorphisms of genes coding for ghrelin and its receptor in relation to anthropometry, circulating levels of IGF-I and IGFBP-3, and breast cancer risk: a case–control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC). Carcinogenesis. 2008;29(7):1360-6.
• 14. Pabalan NA, Seim I, Jarjanazi H, Chopin LK. Associations between ghrelin and ghrelin receptor polymorphisms and cancer in Caucasian populations: a meta-analysis. BMC genetics. 2014;15(1):1-8.
• 15. Wagner K, Hemminki K, Grzybowska E, Klaes R, Burwinkel B, Bugert P, et al. Polymorphisms in genes involved in GH1 release and their association with breast cancer risk. Carcinogenesis. 2006;27(9):1867-75.
• 16. Feigelson HS, Teras LR, Diver WR, Tang W, Patel AV, Stevens VL, et al. Genetic variation in candidate obesity genes ADRB2, ADRB3, Ghrl, HSD11B1, IRS1, IRS2, and SHC1 and risk for breast cancer in the Cancer Prevention Study II. Breast Cancer Res 2008; 10:R57. doi:10.1186/bcr2114
• 17. Slattery ML, Lundgreen A, Hines L, Wolff RK, Torres-Mejia G, Baumgartner KN, et al. Energy homeostasis genes and breast cancer risk: the influence of ancestry, body size, and menopausal status, the breast cancer health disparities study. Cancer Epidemiol 2015; 39:1113–22. doi:10.1016/j.canep.2015.08.012
• 18. Pellatt AJ, Lundgreen A, Wolff RK, Hines L, John EM, Slattery ML. Energy homeostasis genes and survival after breast cancer diagnosis: the Breast Cancer Health Disparities Study. Cancer Causes Control 2016; 27:47–57. doi:10.1007/ s10552-015-0681-6
• 19. Karim R, Stanczyk FZ, Brinton RD, Rettberg J, Hodis HN, Mack WJ. Association of endogenous sex hormones with adipokines and ghrelin in postmenopausal women. The Journal of Clinical Endocrinology & Metabolism. 2015;100(2):508-15.
• 20. Au CC, Furness JB, Brown KA. Ghrelin and breast cancer: emerging roles in obesity, estrogen regulation, and cancer. Frontiers in oncology. 2017;6:265
• 21. Gronberg M, Fjallskog ML, Jirstrom K, Janson ET. Expression of ghrelin is correlated to a favorable outcome in invasive breast cancer. Acta Oncol 2012; 51:386–93. doi: 10.3109/0284186X.2011.631576
• 22. Öztürk B, Kutlutürk F, Sezer E. Üç farklı solid tümörde serum adiponektin düzeyleri. Türk Diyab Obez 2018;2: 65-71.
• 23. Tian C, Zhang L, Hu D, Ji J. Ghrelin induces gastric cancer cell proliferation, migration, and invasion through GHS-R/NF- κB signaling pathway. Molecular and cellular biochemistry. 2013;382(1):163-72
• 24. Dieudonne M-N, Bussiere M, Dos Santos E, Leneveu M-C, Giudicelli Y, Pecquery R. Adiponectin mediates antiproliferative and apoptotic responses in human MCF7 breast cancer cells. Biochemical and biophysical research communications. 2006;345(1):271-9.