Impact of therapy with a selective progesterone receptor modulator on the synthesis of factors that regulate apoptosis and proteolysis in the myomatous nodules of patients with large leiomyoma
Objective. To determine the in vivo molecular mechanisms of action of ulipristal acetate on the cell apoptosis of myomatous nodules and on the proteolysis of extracellular matrix components and to identify the features of a tumor cell response to the drug during its therapy showing varying clinical efficacy.Malyshkina A.I., Voronin D.N., Antsiferova Yu.S., Nagornyi S.N., Kirsanov A.N.
Subjects and methods. A total of 32 women with uterine leiomyoma (17 had not been preoperatively prepared and 15 women had preoperatively received ulipristal acetate 5 mg daily for 3 months) were examined. PCR was used to determine XIAP, PPARy, PTEN, and MMP-2 mRNA expression levels in the biopsies of the myometrium and myomatous nodules.
Results. The drug-untreated patients showed a higher XIAP, PPARy, PTEN, and MMP-2 mRNA expression in the myomatous nodes than in the myometrium. The synthesis of XIAP and MMP-2 decreased and the expression of PPARy mRNA increased in the leiomyomas of the treated women as compared to those of the untreated ones. The ulipristal acetate-induced reduction in nodular sizes was associated with the highest rates of PPARy and PTEN synthesis in the tumor.
Conclusion. The ulipristal acetate-induced reduction in uterine leiomyoma sizes occurs due to the induction of apoptosis in the tumor, by increasing the synthesis of the pro-apoptotic factors PPARy and PTEN.
Keywords
uterine leiomyoma
selective progesterone receptor modulators
ulipristal acetate
apoptosis
XIAP
PPARγ
PTEN
matrix metalloprotenase-2
Supplementary Materials
- Table 1. Characteristic of the mRNAs expression of factors, regulating apoptosis and invasion, in the myometrium and leiomyoma tissue of patients, treated with ulipristal acetate in the preoperative period.
- Table 2. Characteristic of the mRNAs expression of factors, regulating apoptosis and invasion, in the leiomyoma tissue of patients with different tumor size dynamic after treatment with ulipristal acetate
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Received 08.04.2016
Accepted 27.05.2016
About the Authors
Malyshkina Anna Ivanovna, MD, the director of V.N. Gorodkov Ivanovo Research Institute of Maternity and Childhood, Ministry of Health of Russia.153731, Russia, Ivanovo, Pobedy str. 20. Tel.: +74932336263. E-mail: ivniimid@mail.ru
Voronin Dmitry Nikolayevich, PhD, scientific worker of the laboratory of clinical immunology, V.N. Gorodkov Ivanovo Research Institute of Maternity and Childhood,
Ministry of Health of Russia. 153731, Russia, Ivanovo, Pobedy str. 20. Tel.: +74932338320. E-mail: niimid.immune@mail.ru
Antsiferova Yulia Stanislavovna, BD, senior scientific worker of the laboratory of clinical immunology, V.N. Gorodkov Ivanovo Research Institute of Maternity and Childhood, Ministry of Health of Russia. 153731, Russia, Ivanovo, Pobedy str. 20. Tel.: +74932338320. E-mail: niimid.immune@mail.ru
Nagornyi Sergey Nikolayevich, radiologist of Radiology diagnostic Department, V.N. Gorodkov Ivanovo Research Institute of Maternity and Childhood,
Ministry of Health of Russia. 153731, Russia, Ivanovo, Pobedy str. 20. Tel.: +74932338320. E-mail: nagornomu@gmail.com
Kirsanov Aleksey Nikolayevich, PhD, obstetrician-gynecologist of the 4th gynecological department, V.N. Gorodkov Ivanovo Research Institute of Maternity and Childhood, Ministry of Health of Russia. 153731, Russia, Ivanovo, Pobedy str. 20. Tel.: +74932336263. E-mail: drkirsanov@gmail.com
For citations: Malyshkina A.I., Voronin D.N., Antsiferova Yu.S., Nagornyi S.N., Kirsanov A.N. Impact of therapy with a selective progesterone receptor modulator on the synthesis of factors that regulate apoptosis and proteolysis in the myomatous nodules of patients with large leiomyoma. Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2017; (2): 64-70. (in Russian)
http://dx.doi.org/10.18565/aig.2017.2.64-70
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