Oral Contraceptive Steroids Promote Papillary Thyroid Cancer Metastasis by Targeting Angiogenesis and Epithelial-Mesenchymal Transition

Dehghan, Mohammad Hossein; Ashrafi, Mohammad Reza; Hedayati, Mehdi; Shivaee, Setareh; Rajabi, Sadegh

doi:10.22088/IJMCM.BUMS.10.3.218

Volume 10, Issue 3 (Int J Mol Cell Med 2021) Int J Mol Cell Med 2021, 10(3): 218-226 | Back to browse issues page

‎ 10.22088/IJMCM.BUMS.10.3.218

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Dehghan M H, Ashrafi M R, Hedayati M, Shivaee S, Rajabi S. Oral Contraceptive Steroids Promote Papillary Thyroid Cancer Metastasis by Targeting Angiogenesis and Epithelial-Mesenchymal Transition. Int J Mol Cell Med 2021; 10 (3) :218-226
URL: http://ijmcmed.org/article-1-1650-en.html

Oral Contraceptive Steroids Promote Papillary Thyroid Cancer Metastasis by Targeting Angiogenesis and Epithelial-Mesenchymal Transition

Mohammad Hossein Dehghan¹

, Mohammad Reza Ashrafi²

, Mehdi Hedayati³

, Setareh Shivaee³

, Sadegh Rajabi⁴

1- Biochemistry Department, School of Medicine, Alborz University of Medical Sciences, Karaj, Iran.
2- Department of Biochemistry, Afzalipoor Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran.
3- Cellular and Molecular Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
4- Traditional Medicine and Materia Medica Research Center (TMRC), Shahid Beheshti University of Medical Sciences, Tehran, Iran. , Sadegh.rajabi2017@gmail.com

Abstract: (5094 Views)

Thyroid cancer is the most prevalent type of endocrine malignancy with the highest incidence rate among women under 45 years old. Ethinylestradiol (EE) and levonorgestrel (LNG) are two steroid components of low-dose oral contraceptives used all over the world. In this study, we aimed to examine the possible effects of the combination of these two steroids on metastasis and angiogenic factors in BCPAP papillary thyroid cancer (PTC) cell line. After treatment of BCPAP cells with the combination of 20 nM EE and 90 nM LNG, mRNA expression levels of long noncoding RNAs HOTAIR and MALAT1, angiogenic and antiangiogenic gene markers VEGFA and THBS1, and epithelial-mesenchymal transition (EMT) biomarkers CDH1, CDH2, FN1, and VIM were analyzed by real-time PCR. Additionally, the protein expression of VEGFA was semiquantified by Western blotting. Results showed that the combination of LNG and EE significantly elevated the level of VEGFA protein and mRNA expression of VEGFA, MALAT1, HOTAIR, CDH2, FN1, and VIM genes while decreased CDH1 gene expression but had no marked effect on the expression of THBS1 gene in comparison with the control group. Also, our results suggest that LNG and EE may increase the metastatic and migratory properties of BCPAP cells via modulating angiogenic and EMT biomarkers. These data may highlight the potential of exogenous steroids in the advancement of PTC tumors.

Keywords: Papillary thyroid cancer, metastasis, migration, angiogenesis, epithelial-mesenchymal transition

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Type of Study: Original Article | Subject: Cell Biology
Received: 2021/05/11 | Accepted: 2021/08/25 | Published: 2022/01/10