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Effects of Fenformin On Cell Viability and FGFR2 Expression in PC-3 Human Prostate Cancer Cell Line

Year 2023, Volume: 10 Issue: 2, 84 - 89, 21.08.2023
https://doi.org/10.47572/muskutd.1024832

Abstract

Prostate cancer is the second most common cause of cancer-related death in men. New drugs are needed to treat prostate cancer due to the development of resistance to chemotherapeutics. Although phenformin is a biguanide antidiabetic drug, it also has anticarcinogenic effects. Fibroblast growth factor receptor 2 (FGFR2) is a membrane receptor that promotes cell proliferation and differentiation. Our study; was aimed to investigate the effects of phenformin on FGFR2 in PC-3 human prostate cancer cells. Experimental groups; control groups were administered 1 mM, 2 mM, 5 mM, and 10 mM phenformin. WST-1 cell viability analysis was performed 24 hours after phenformin administration, and H-Score was calculated after immunocytochemical staining for FGFR2. The SPSS program was used for statistical analysis. According to the WST-1 analysis; when the control group and the 5 mM phenformin group, the control group with the 10 mM phenformin group, and the 1 mM phenformin group with the 10 mM phenformin group were compared, a statistically significant decrease in cell viability was detected (p<0.05, for all). According to the H-Score results; The decrease in FGFR2 expression between control group and 5 mM phenformin group, control group and 10 mM phenformin group, 1 mM phenformin group and 5 mM phenformin group, and 1 mM phenformin group and 10 mM phenformin group was statistically significant (p<0.05, for all). Our study showed that phenformin has dose dependent effect in reducing FGFR2 expression from PC-3 human prostate cancer cells and inhibiting cell proliferation, and 10 mM phenformin was the most effective dose.

References

  • 1. Rawla P. Epidemiology of prostate cancer. World J Oncol. 2019;10(2):63.
  • 2. Mansoori B, Mohammadi A, Davudian S, et al. The different mechanisms of cancer drug resistance: a brief review. Adv Pharm Bull. 2017;7(3):339.
  • 3. Tai S, Sun Y, Squires JM, et al. PC3 is a cell line characteristic of prostatic small cell carcinoma. Prostate. 2011;71(15):1668-79.
  • 4. Vara-Ciruelos D, Dandapani M, Russell FM, et al. Phenformin, but not metformin, delays development of t cell acute lymphoblastic leukemia/lymphoma via cell-autonomous ampk activation. Cell Rep. 2019;27(3): 690-8.
  • 5. McKendry JB, Kuwayti K, Rado PP. Clinical experience with DBI (phenformin) in the management of diabetes. Can Med Assoc J. 1959;80(10):773-8.
  • 6. Pollak M. Metformin and other biguanides in oncology: advancing the research agenda. Cancer Prev Res (Phila). 2010;3(9):1060-5.
  • 7. Decensi A, Puntoni M, Goodwin P, et al. Metformin and cancer risk in diabetic patients: a systematic review and meta-analysis. Cancer Prev Res. 2010;3(11):1451–61.
  • 8. Appleyard MV, Murray KE, Coates PJ, et al. Phenformin as prophylaxis and therapy in breast cancer xenografts. Br J Cancer. 2012;106(6):1117–22.
  • 9. Huang X, Wullschleger S, Shpiro N, et al. Important role of the LKB1-AMPK pathway in suppressing tumorigenesis in PTEN-deficient mice. Biochem J. 2008;412(2):211–21.
  • 10. García Rubiño M, Carrillo E, Ruiz Alcalá G, et al. Phenformin as an anticancer agent: challenges and prospects. Int J Mol Sci. 2019;20(13):3316.
  • 11. Park JH, Kim YH, Park EH, et al. Effects of metformin and phenformin on apoptosis and epithelial‐mesenchymal transition in chemoresistant rectal cancer. Cancer Sci. 2019;110(9):2834-45.
  • 12. Jackson AL, Sun W, Kilgore J, et al. Phenformin has anti-tumorigenic effects in human ovarian cancer cells and in an orthotopic mouse model of serous ovarian cancer. Oncotarget. 2017;8(59):100113.
  • 13. Jafari-Gharabaghlou D, Pilehvar-Soltanahmadi Y, Dadashpour M, et al. Combination of metformin and phenformin synergistically inhibits proliferation and hTERT expression in human breast cancer cells. Iran J Basic Med Sci. 2018;21(11):1167.
  • 14. Huang Y, Zhou S, He C, et al. Phenformin alone or combined with gefitinib inhibits bladder cancer via AMPK and EGFR pathways. Cancer Commun. 2018;38(1):1-4.
  • 15. Coperchini F, Croce L, Denegri M, et al. The anti-cancer effects of phenformin in thyroid cancer cell lines and in normal thyrocytes. Oncotarget. 2019;10(60):6432.
  • 16. Fu YT, Zheng HB, Zhang DQ, et al. MicroRNA-1266 suppresses papillary thyroid carcinoma cell metastasis and growth via targeting FGFR2. Eur Rev Med Pharmacol Sci. 2018;22(11):3430-8.
  • 17. Grose R, Dickson C. Fibroblast growth factor signaling in tumorigenesis. Cytokine Growth Factor Rev. 2005;16(2):179-86.
  • 18. Larrieu-Lahargue F, Welm AL, Bouchecareilh M, et al. Blocking fibroblast growth factor receptor signaling inhibits tumor growth, lymphangiogenesis, and metastasis. PLoS One. 2012;7(6):e39540.
  • 19. Bai A, Meetze K, Vo NY, et al. GP369, an FGFR2-IIIb-specific antibody, exhibits potent antitumor activity against human cancers driven by activated FGFR2 signaling. Cancer Res. 2010;70(19):7630-9.
  • 20. Tu DG, Yu Y, Lee CH, et al. Hinokitiol inhibits vasculogenic mimicry activity of breast cancer stem/progenitor cells through proteasome mediated degradation of epidermal growth factor receptor. Oncol Lett. 2016;11(4):2934-40.
  • 21. Specht E, Kaemmerer D, Sänger J, et al. Comparison of immunoreactive score, HER2/neu score and H score for the immunohistochemical evaluation of somatostatin receptors in bronchopulmonary neuroendocrine neoplasms. Histopathology. 2015;67(3):368-77.
  • 22. Chabner BA, Roberts TG. Chemotherapy and the war on cancer. Nat Rev Cancer. 2005;5(1):65-72.
  • 23. Leone A, Di Gennaro E, Bruzzese F, et al. New perspective for an old antidiabetic drug: metformin as anticancer agent. Adv Nutr Cancer. 2014:355-76.
  • 24. Scappaticcio L, Maiorino MI, Bellastella G, et al. Insights into the relationships between diabetes, prediabetes, and cancer. Endocrine. 2017;56(2):231-9.
  • 25. Tokajuk A, Krzyżanowska-Grycel E, Tokajuk A, et al. Antidiabetic drugs and risk of cancer. Pharmacol Rep. 2015;67(6):1240-50.
  • 26. Totten SP, Im YK, Cepeda Cañedo EN et al. STAT1 potentiates oxidative stress revealing a targetable vulnerability that increases phenformin efficacy in breast cancer. Nat Commun. 2021;12(1):1-20.
  • 27. Zhou S, Xu L, Cao M, et al. Anticancer properties of novel pyrazole‐containing biguanide derivatives with activating the adenosine monophosphate‐activated protein kinase signaling pathway. Archiv der Pharmazie. 2019;352(9):1900075.
  • 28. Di Magno L, Manni S, Di Pastena F, et al. Phenformin inhibits Hedgehog-dependent tumor growth through a complex ı-ındependent redox/corepressor module. Cell Rep. 2020;30(6):1735-52.e7.
  • 29. Orecchioni S, Reggiani F, Talarico G, et al. The biguanides metformin and phenformin inhibit angiogenesis, local and metastatic growth of breast cancer by targeting both neoplastic and microenvironment cells. Int J Cancer. 2015;136(6):E534-44.
  • 30. Guo Z, Zhao M, Howard EW, Zhao Q, et al. Phenformin inhibits growth and epithelial-mesenchymal transition of ErbB2-overexpressing breast cancer cells through targeting the IGF1R pathway. Oncotarget. 2017;8(36):60342-57.
  • 31. Peng M, Deng J, Zhou S, et al. Dual inhibition of pirarubicin-induced AKT and ERK activations by phenformin sensitively suppresses bladder cancer growth. Front Pharmacol. 2019;10:1159.
  • 32. Wang Y, Meng Y, Zhang S, et al. Phenformin and metformin inhibit growth and migration of LN229 glioma cells in vitro and in vivo. OncoTargets Ther. 2018;11:6039-48.
  • 33. Petiot A, Conti FJ, Grose R, et al. A crucial role for Fgfr2-IIIb signalling in epidermal development and hair follicle patterning. Development. 2003;130(22):5493–501.
  • 34. Revest JM, Suniara RK, Kerr K, et al. Development of the thymus requires signaling through the fibroblast growth factor receptor R2-IIIb. J Immunol. 2001;167(4):1954–61.
  • 35. Yu K, Xu J, Liu Z, et al. Conditional inactivation of FGF receptor 2 reveals an essential role for FGF signaling in the regulation of osteoblast function and bone growth. Development. 2003;130(13):3063–74.
  • 36. Colvin JS, Bohne BA, Harding GW, et al. Skeletal over growth and deafness in mice lacking fibroblast growth factor receptor 3. Nat Genet. 1996;12(4):390–7.
  • 37. Kunii K, Davis L, Gorenstein J, et al. FGFR2-amplified gastric cancer cell lines require FGFR2 and Erbb3 signaling for growth and survival. Cancer Res. 2008;68(7):2340- 8.
  • 38. Moffa AB, Ethier SP. Differential signal transduction of alternatively spliced FGFR2 variants expressed in human mammary epithelial cells. J Cell Physiol. 2007;210(3):720-31.
  • 39. Tyulyandina A, Demidova I, Gikalo M, et al. Role of FGFR2 amplification in prognosis of patients with ovarian cancer. Annals of Oncology. 2018;29:viii354-5.
  • 40. Katoh Y, Katoh M. FGFR2-related pathogenesis and FGFR2-targeted therapeutics. Int J Mol Med. 2009;23(3):307-11.
  • 41. Bailey CJ. Biguanides and NIDDM. Diabetes care. 1992;15(6):755-72.
  • 42. Janzer A, German NJ, Gonzalez-Herrera KN, et al. Metformin and phenformin deplete tricarboxylic acid cycle and glycolytic intermediates during cell transformation and NTPs in cancer stem cells. Proc Natl Acad Sci. 2014;111(29):10574-9.
  • 43. Miskimins WK, Ahn HJ, Kim JY, et al. Synergistic anti-cancer effect of phenformin and oxamate. PloS one. 2014;9(1):e85576.

PC-3 İnsan Prostat Kanseri Hücrelerinde Fenforminin Hücre Canlılığı ve FGFR2 Ekspresyonu Üzerine Etkileri

Year 2023, Volume: 10 Issue: 2, 84 - 89, 21.08.2023
https://doi.org/10.47572/muskutd.1024832

Abstract

Prostat kanseri, erkeklerde kansere bağlı ölümlerin ikinci en sık nedenidir. Kemoterapötiklere direnç gelişmesi nedeniyle prostat kanserini tedavi etmek için yeni ilaçlara ihtiyaç vardır. Fenformin biguanid grubu antidiyabetik bir ilaçtır ve antikanserojen etkileri de vardır. Fibroblast büyüme faktörü reseptörü 2 (FGFR2), hücre proliferasyonunu ve farklılaşmasını destekleyen bir membran reseptörüdür. Çalışmamızda; PC-3 insan prostat kanseri hücrelerinde fenforminin FGFR2 üzerinden etkilerinin araştırılması amaçlandı. Deney grupları; kontrol grubu, 1 mM, 2 mM, 5 mM ve 10 mM fenformin uygulanan gruplar idi. Fenformin uygulamalarından 24 saat sonra WST-1 hücre canlılığı analizi yapıldı, ayrıca FGFR2 için immunositokimyasal boyamadan sonra H-Skoru hesaplandı. İstatistiksel analizler için SPSS programı kullanıldı. WST-1 analizi sonuçlarına göre; kontrol grubu ile 5 mM fenformin grubu, kontrol grubu ile 10 mM fenformin grubu ve 1 mM fenformin grubu ile 10 mM fenformin grubu karşılaştırıldığında hücre canlılığında istatistiksel olarak anlamlı derecede azalma tespit edildi (p<0.05, hepsi için). H-Skoru sonuçlarına göre; kontrol grubu ve 5 mM fenformin grubu, kontrol grubu ile 10 mM fenformin grubu, 1 mM fenformin grubu ile 5 mM fenformin grubu ve 1 mM fenformin grubu ile 10 mM fenformin grubu arasındaki FGFR2 ekspresyonunun azalması istatistiksel olarak anlamlıydı (p<0.05, hepsi için). Çalışmamızda fenformin, doza bağlı olarak PC-3 insan prostat kanseri hücreleri üzerinde FGFR2 ekspresyonunu azaltıcı ve hücre proliferasyonunu inhibe edici etkiler göstermiştir. En etkili dozun 10 mM fenformin olduğu tespit edilmiştir.

References

  • 1. Rawla P. Epidemiology of prostate cancer. World J Oncol. 2019;10(2):63.
  • 2. Mansoori B, Mohammadi A, Davudian S, et al. The different mechanisms of cancer drug resistance: a brief review. Adv Pharm Bull. 2017;7(3):339.
  • 3. Tai S, Sun Y, Squires JM, et al. PC3 is a cell line characteristic of prostatic small cell carcinoma. Prostate. 2011;71(15):1668-79.
  • 4. Vara-Ciruelos D, Dandapani M, Russell FM, et al. Phenformin, but not metformin, delays development of t cell acute lymphoblastic leukemia/lymphoma via cell-autonomous ampk activation. Cell Rep. 2019;27(3): 690-8.
  • 5. McKendry JB, Kuwayti K, Rado PP. Clinical experience with DBI (phenformin) in the management of diabetes. Can Med Assoc J. 1959;80(10):773-8.
  • 6. Pollak M. Metformin and other biguanides in oncology: advancing the research agenda. Cancer Prev Res (Phila). 2010;3(9):1060-5.
  • 7. Decensi A, Puntoni M, Goodwin P, et al. Metformin and cancer risk in diabetic patients: a systematic review and meta-analysis. Cancer Prev Res. 2010;3(11):1451–61.
  • 8. Appleyard MV, Murray KE, Coates PJ, et al. Phenformin as prophylaxis and therapy in breast cancer xenografts. Br J Cancer. 2012;106(6):1117–22.
  • 9. Huang X, Wullschleger S, Shpiro N, et al. Important role of the LKB1-AMPK pathway in suppressing tumorigenesis in PTEN-deficient mice. Biochem J. 2008;412(2):211–21.
  • 10. García Rubiño M, Carrillo E, Ruiz Alcalá G, et al. Phenformin as an anticancer agent: challenges and prospects. Int J Mol Sci. 2019;20(13):3316.
  • 11. Park JH, Kim YH, Park EH, et al. Effects of metformin and phenformin on apoptosis and epithelial‐mesenchymal transition in chemoresistant rectal cancer. Cancer Sci. 2019;110(9):2834-45.
  • 12. Jackson AL, Sun W, Kilgore J, et al. Phenformin has anti-tumorigenic effects in human ovarian cancer cells and in an orthotopic mouse model of serous ovarian cancer. Oncotarget. 2017;8(59):100113.
  • 13. Jafari-Gharabaghlou D, Pilehvar-Soltanahmadi Y, Dadashpour M, et al. Combination of metformin and phenformin synergistically inhibits proliferation and hTERT expression in human breast cancer cells. Iran J Basic Med Sci. 2018;21(11):1167.
  • 14. Huang Y, Zhou S, He C, et al. Phenformin alone or combined with gefitinib inhibits bladder cancer via AMPK and EGFR pathways. Cancer Commun. 2018;38(1):1-4.
  • 15. Coperchini F, Croce L, Denegri M, et al. The anti-cancer effects of phenformin in thyroid cancer cell lines and in normal thyrocytes. Oncotarget. 2019;10(60):6432.
  • 16. Fu YT, Zheng HB, Zhang DQ, et al. MicroRNA-1266 suppresses papillary thyroid carcinoma cell metastasis and growth via targeting FGFR2. Eur Rev Med Pharmacol Sci. 2018;22(11):3430-8.
  • 17. Grose R, Dickson C. Fibroblast growth factor signaling in tumorigenesis. Cytokine Growth Factor Rev. 2005;16(2):179-86.
  • 18. Larrieu-Lahargue F, Welm AL, Bouchecareilh M, et al. Blocking fibroblast growth factor receptor signaling inhibits tumor growth, lymphangiogenesis, and metastasis. PLoS One. 2012;7(6):e39540.
  • 19. Bai A, Meetze K, Vo NY, et al. GP369, an FGFR2-IIIb-specific antibody, exhibits potent antitumor activity against human cancers driven by activated FGFR2 signaling. Cancer Res. 2010;70(19):7630-9.
  • 20. Tu DG, Yu Y, Lee CH, et al. Hinokitiol inhibits vasculogenic mimicry activity of breast cancer stem/progenitor cells through proteasome mediated degradation of epidermal growth factor receptor. Oncol Lett. 2016;11(4):2934-40.
  • 21. Specht E, Kaemmerer D, Sänger J, et al. Comparison of immunoreactive score, HER2/neu score and H score for the immunohistochemical evaluation of somatostatin receptors in bronchopulmonary neuroendocrine neoplasms. Histopathology. 2015;67(3):368-77.
  • 22. Chabner BA, Roberts TG. Chemotherapy and the war on cancer. Nat Rev Cancer. 2005;5(1):65-72.
  • 23. Leone A, Di Gennaro E, Bruzzese F, et al. New perspective for an old antidiabetic drug: metformin as anticancer agent. Adv Nutr Cancer. 2014:355-76.
  • 24. Scappaticcio L, Maiorino MI, Bellastella G, et al. Insights into the relationships between diabetes, prediabetes, and cancer. Endocrine. 2017;56(2):231-9.
  • 25. Tokajuk A, Krzyżanowska-Grycel E, Tokajuk A, et al. Antidiabetic drugs and risk of cancer. Pharmacol Rep. 2015;67(6):1240-50.
  • 26. Totten SP, Im YK, Cepeda Cañedo EN et al. STAT1 potentiates oxidative stress revealing a targetable vulnerability that increases phenformin efficacy in breast cancer. Nat Commun. 2021;12(1):1-20.
  • 27. Zhou S, Xu L, Cao M, et al. Anticancer properties of novel pyrazole‐containing biguanide derivatives with activating the adenosine monophosphate‐activated protein kinase signaling pathway. Archiv der Pharmazie. 2019;352(9):1900075.
  • 28. Di Magno L, Manni S, Di Pastena F, et al. Phenformin inhibits Hedgehog-dependent tumor growth through a complex ı-ındependent redox/corepressor module. Cell Rep. 2020;30(6):1735-52.e7.
  • 29. Orecchioni S, Reggiani F, Talarico G, et al. The biguanides metformin and phenformin inhibit angiogenesis, local and metastatic growth of breast cancer by targeting both neoplastic and microenvironment cells. Int J Cancer. 2015;136(6):E534-44.
  • 30. Guo Z, Zhao M, Howard EW, Zhao Q, et al. Phenformin inhibits growth and epithelial-mesenchymal transition of ErbB2-overexpressing breast cancer cells through targeting the IGF1R pathway. Oncotarget. 2017;8(36):60342-57.
  • 31. Peng M, Deng J, Zhou S, et al. Dual inhibition of pirarubicin-induced AKT and ERK activations by phenformin sensitively suppresses bladder cancer growth. Front Pharmacol. 2019;10:1159.
  • 32. Wang Y, Meng Y, Zhang S, et al. Phenformin and metformin inhibit growth and migration of LN229 glioma cells in vitro and in vivo. OncoTargets Ther. 2018;11:6039-48.
  • 33. Petiot A, Conti FJ, Grose R, et al. A crucial role for Fgfr2-IIIb signalling in epidermal development and hair follicle patterning. Development. 2003;130(22):5493–501.
  • 34. Revest JM, Suniara RK, Kerr K, et al. Development of the thymus requires signaling through the fibroblast growth factor receptor R2-IIIb. J Immunol. 2001;167(4):1954–61.
  • 35. Yu K, Xu J, Liu Z, et al. Conditional inactivation of FGF receptor 2 reveals an essential role for FGF signaling in the regulation of osteoblast function and bone growth. Development. 2003;130(13):3063–74.
  • 36. Colvin JS, Bohne BA, Harding GW, et al. Skeletal over growth and deafness in mice lacking fibroblast growth factor receptor 3. Nat Genet. 1996;12(4):390–7.
  • 37. Kunii K, Davis L, Gorenstein J, et al. FGFR2-amplified gastric cancer cell lines require FGFR2 and Erbb3 signaling for growth and survival. Cancer Res. 2008;68(7):2340- 8.
  • 38. Moffa AB, Ethier SP. Differential signal transduction of alternatively spliced FGFR2 variants expressed in human mammary epithelial cells. J Cell Physiol. 2007;210(3):720-31.
  • 39. Tyulyandina A, Demidova I, Gikalo M, et al. Role of FGFR2 amplification in prognosis of patients with ovarian cancer. Annals of Oncology. 2018;29:viii354-5.
  • 40. Katoh Y, Katoh M. FGFR2-related pathogenesis and FGFR2-targeted therapeutics. Int J Mol Med. 2009;23(3):307-11.
  • 41. Bailey CJ. Biguanides and NIDDM. Diabetes care. 1992;15(6):755-72.
  • 42. Janzer A, German NJ, Gonzalez-Herrera KN, et al. Metformin and phenformin deplete tricarboxylic acid cycle and glycolytic intermediates during cell transformation and NTPs in cancer stem cells. Proc Natl Acad Sci. 2014;111(29):10574-9.
  • 43. Miskimins WK, Ahn HJ, Kim JY, et al. Synergistic anti-cancer effect of phenformin and oxamate. PloS one. 2014;9(1):e85576.
There are 43 citations in total.

Details

Primary Language Turkish
Subjects Clinical Sciences
Journal Section Original Article
Authors

Dilan Çetinavcı 0000-0002-4148-7711

Melike Özgül Önal 0000-0001-6710-5729

Gürkan Yiğittürk 0000-0002-5315-253X

Volkan Yaşar This is me 0000-0003-3497-1238

Hülya Elbe 0000-0002-1254-0683

Feral Öztürk 0000-0003-1207-5213

Publication Date August 21, 2023
Submission Date November 17, 2021
Published in Issue Year 2023 Volume: 10 Issue: 2

Cite

APA Çetinavcı, D., Özgül Önal, M., Yiğittürk, G., Yaşar, V., et al. (2023). PC-3 İnsan Prostat Kanseri Hücrelerinde Fenforminin Hücre Canlılığı ve FGFR2 Ekspresyonu Üzerine Etkileri. Muğla Sıtkı Koçman Üniversitesi Tıp Dergisi, 10(2), 84-89. https://doi.org/10.47572/muskutd.1024832
AMA Çetinavcı D, Özgül Önal M, Yiğittürk G, Yaşar V, Elbe H, Öztürk F. PC-3 İnsan Prostat Kanseri Hücrelerinde Fenforminin Hücre Canlılığı ve FGFR2 Ekspresyonu Üzerine Etkileri. MMJ. August 2023;10(2):84-89. doi:10.47572/muskutd.1024832
Chicago Çetinavcı, Dilan, Melike Özgül Önal, Gürkan Yiğittürk, Volkan Yaşar, Hülya Elbe, and Feral Öztürk. “PC-3 İnsan Prostat Kanseri Hücrelerinde Fenforminin Hücre Canlılığı Ve FGFR2 Ekspresyonu Üzerine Etkileri”. Muğla Sıtkı Koçman Üniversitesi Tıp Dergisi 10, no. 2 (August 2023): 84-89. https://doi.org/10.47572/muskutd.1024832.
EndNote Çetinavcı D, Özgül Önal M, Yiğittürk G, Yaşar V, Elbe H, Öztürk F (August 1, 2023) PC-3 İnsan Prostat Kanseri Hücrelerinde Fenforminin Hücre Canlılığı ve FGFR2 Ekspresyonu Üzerine Etkileri. Muğla Sıtkı Koçman Üniversitesi Tıp Dergisi 10 2 84–89.
IEEE D. Çetinavcı, M. Özgül Önal, G. Yiğittürk, V. Yaşar, H. Elbe, and F. Öztürk, “PC-3 İnsan Prostat Kanseri Hücrelerinde Fenforminin Hücre Canlılığı ve FGFR2 Ekspresyonu Üzerine Etkileri”, MMJ, vol. 10, no. 2, pp. 84–89, 2023, doi: 10.47572/muskutd.1024832.
ISNAD Çetinavcı, Dilan et al. “PC-3 İnsan Prostat Kanseri Hücrelerinde Fenforminin Hücre Canlılığı Ve FGFR2 Ekspresyonu Üzerine Etkileri”. Muğla Sıtkı Koçman Üniversitesi Tıp Dergisi 10/2 (August 2023), 84-89. https://doi.org/10.47572/muskutd.1024832.
JAMA Çetinavcı D, Özgül Önal M, Yiğittürk G, Yaşar V, Elbe H, Öztürk F. PC-3 İnsan Prostat Kanseri Hücrelerinde Fenforminin Hücre Canlılığı ve FGFR2 Ekspresyonu Üzerine Etkileri. MMJ. 2023;10:84–89.
MLA Çetinavcı, Dilan et al. “PC-3 İnsan Prostat Kanseri Hücrelerinde Fenforminin Hücre Canlılığı Ve FGFR2 Ekspresyonu Üzerine Etkileri”. Muğla Sıtkı Koçman Üniversitesi Tıp Dergisi, vol. 10, no. 2, 2023, pp. 84-89, doi:10.47572/muskutd.1024832.
Vancouver Çetinavcı D, Özgül Önal M, Yiğittürk G, Yaşar V, Elbe H, Öztürk F. PC-3 İnsan Prostat Kanseri Hücrelerinde Fenforminin Hücre Canlılığı ve FGFR2 Ekspresyonu Üzerine Etkileri. MMJ. 2023;10(2):84-9.