|
|
|
| Effect of Down-regulation of MMP-2 by Quercetin on the Migration and Invasion of Uterine Fibroids Cells through the cAMP Signaling Pathway |
| LIN Shu-ping, ZOU Xiao-fen |
| Longyan First Affiliated Hospital of Fujian Medical University, Longyan Fujian 364000, China |
|
|
|
|
Abstract Objective: To investigate the effect of down-regulation of matrix metalloproteinase-2 (MMP-2) by down-regulating the cyclic adenosine monophosphate (cAMP) signaling pathway on the migration and invasion of uterine fibroids cells. Methods: A total of 65 female SD rats were randomly divided into five groups after being adaptively fed for 7 d. Except for the blank group, the remaining four groups of rats were injected with 0.05 mg/(100 g·d) estradiol benzoate and 0.5 mg/(100g·d) progesterone into the muscle to establish a uterine fibroids rat model. After successful modeling, the blank group and model group were given 200 mg/(kg·d) physiological saline by gavage, the low-dose group was given 100 mg/(kg·d) mifepristone by gavage, the medium-dose group was given 200 mg/(kg·d) mifepristone by gavage, and the high-dose group was given 300 mg/(kg·d) mifepristone by gavage. After continuous gavage treatment for 21 d, serum and uterine tissues were collected from rats to observe and compare the expression levels of MMP-2 mRNA, TIMP-2 mRNA, estradiol(E2), cAMP signaling pathway related proteins, and the migration and invasive ability of uterine fibroids cells in the five groups of rats. Results: The expression levels of MMP-2 mRNA and E2 in the high-dose group were lower than those in the low-dose group and the medium-dose group, and the expression level of TIMP-2 mRNA was higher than that in the low-dose group and the medium-dose group(P<0.05). The number of cell migration in a single visual field of rats in the high-dose group was lower than that in the low-dose group and the medium-dose group (P<0.05). The number of cell invasion in a single visual field of rats in the high-dose group was lower than that in the low-dose group and the medium-dose group (P<0.05). The mRNA expression levels of cAMP, PDE and PK in the high-dose group were higher than those in the low-dose group, and the mRNA expression levels of AC in the high-dose group were lower than those in the low-dose group(P<0.05). The mRNA expression levels of cAMP and PDE in the high-dose group were higher than those in the medium- dose group (P<0.05). Conclusion: Letrozole may down-regulate the expression level of MMP-2 through the cAMP signaling pathway to inhibit the migration and invasion of uterine fibroids cells. With increasing doses of letrozole, its inhibitory effect on the migration and invasion of uterine fibroids cells will be enhanced. However, the optimal dosage of letrozole for inhibiting the migration and invasion of uterine fibroids cells is yet to be determined.
|
|
Received: 15 January 2024
|
|
|
|
Corresponding Authors:
LIN Shu-ping. E-mail: 403384956@qq.com
|
|
|
|
[1] Cheng LC, Li HY, Gong QQ, et al.Global, regional, and national burden of uterine fibroids in the last 30 years: Estimates from the 1990 to 2019 global burden of disease study[J]. Front Med (Lausanne), 2022, 9: 1003605.
[2] Shi Shasha, Yu Chenghao.Progress in the treatment of uterine fibroids[J]. Chinese Journal of Obstetrics and Gynecology, 2020, 35(16): 3122-3125.
[3] Wang Jianhua, Gong Dian, Zhang Jiwang.Expressions of matrix metalloproteinase-2,myosin light chain kinase,and sulfotransferases 1A3 in uterine leiomyoma tis-sues of patients and their correlation with the uterine leiomyoma occurrence[J].Chinese Journal of Family Planning, 2023, 31(2): 429-433.
[4] Sun Qiufeng.Effects of compound curcumin on cAMP-PKA signaling pathway and expression of MMP-2 and TIMP-2 in patients with endometriosis[J]. Journal of Chinese Medicine,2017, 32(9): 1745-1748.
[5] Ashall V, Morton D, Clutton E.A Declaration of Helsinki for animals[J]. Vet Anaesth Analg, 2023, 50(4): 309-314.
[6] Meng Chunyan, Zhang Fuju, Su Yongping.Research progress of letrozole in adjuvant endocrine therapy for breast cancer[J]. Oncology Progress,2021, 19(5): 438-441.
[7] Drishya G, Nambiar J, Shaji SK, et al.RECK and TIMP-2 mediate inhibition of MMP-2 and MMP-9 by Annona muricata[J]. J Biosci, 2020, 45: 89.
[8] Staun-Ram E, Goldman S, Shalev E.Ets-2 and p53 mediate cAMP-induced MMP-2 expression, activity and trophoblast invasion[J]. Reprod Biol Endocrinol, 2009, 7: 135.
[9] Satpathy M, Shao M, Emerson R, et al.Tissue transglutaminase regulates matrix metalloproteinase-2 in ovarian cancer by modulating cAMP-response element-binding protein activity[J]. J Biol Chem, 2009, 284(23): 15390-15399.
[10] Lee C, Lee J, Choi YA, et al.cAMP elevating agents suppress secretory phospholipase A(2)-induced matrix metalloproteinase-2 activation[J]. Biochem Biophys Res Commun, 2006, 340(4): 1278-1283. |
|
|
|
