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Sterol Regulatory Element-Binding Protein–1/Fatty Acid Synthase Involvement in Proliferation Inhibition and Apoptosis Promotion Induced by Progesterone in Endometrial Cancer

Qiu, Chunping MBBS*; Dongol, Samina MBBS*; Lv, Qing-tao PhD; Gao, Ximei MBBS; Jiang, Jie MD, PhD*

International Journal of Gynecological Cancer: November 2013 - Volume 23 - Issue 9 - p 1629–1634
doi: 10.1097/IGC.0000000000000004
Uterine Cancer

Background: The number of endometrial cancer (EC) cases is escalating rapidly, with no evident improvements in survival rates. The downregulation of progesterone receptor, resulting in progestin resistance, is presently a major problem regarding the therapeutic aspect. On the basis of this, we can focus more on the downstream signaling pathways that are controlled by progesterone. Lipid biosynthesis mediated by sterol regulatory element-binding protein–1/fatty acid synthase (SREBP-1/FASN) is of utmost importance to the growth and the proliferation of EC cells, so we hypothesize that SREBP-1/FASN might be involved in suppressing the proliferation and promoting apoptosis in EC cells through the effects induced by progesterone.

Material and Methods: The Cell Counting Kit-8 was used to analyze the growth inhibition ratio of Ishikawa cells upon treatment with megestrol acetate (MA; MA is a progesterone derivative, also known as 17α-acetoxy-6-dehydro-6-methylprogesterone) and to determine the 50% inhibitory concentration. Apoptosis ratio was analyzed by treatment of the cells with MA at 50% inhibitory concentration at different time intervals using Annexin V-FITC/propidium iodide. The protein and messenger RNA levels of SREBP-1 and FASN were compared between the experimental and control groups (MA-treated Ishikawa cells were considered to be the experimental group).

Results: The experimental group showed obvious growth inhibition that was time and concentration dependent. The apoptosis ratio was also significantly higher in the experimental group compared with the control group (P < 0.01). The protein and messenger RNA levels of SREBP-1 and FASN were significantly reduced by MA too.

Conclusions: Sterol regulatory element-binding protein–1/FASN is involved in the proliferation suppression and apoptosis promotion brought about by MA in Ishikawa cells.

*Department of Obstetrics and Gynecology, Qi Lu Hospital, Shangong University, Jinan, Shandong, China; †Department of Pharmaceutical Chemistry, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China; and ‡Physical Examination Centre, Qi Lu Hospital, Shangong University, Jinan, Shandong, China.

Address correspondence and reprint requests to Jie Jiang, MD, PhD, Department of Obstetrics and Gynecology, Qi Lu Hospital, Shandong University, 107 Wenhuaxi Rd, Jinan, 250012. E-mail: qljiangjie@sdu.edu.cn.

Chunping Qiu and Samina Dongol have equally contributed to this study.

This study was accomplished in the cardiovascular laboratory of Qi Lu Hospital of Shandong University and was supported by grants from the National Natural Science Foundation of China (81072121, 81372808 [J.J] and 81173614 [Q.T.L.]) as well as the Science and Technology Development planning of Shandong (2011GSF12122 [X.Z.] and 2012G0021823 [J.J.]).

The authors declare no conflicts of interest.

Received May 22, 2013

Accepted August 20, 2013

© 2013 by the International Gynecologic Cancer Society and the European Society of Gynaecological Oncology.