AK000953 silencing can enhance the killing effect of danazol on uterine fibroids

In: Archives of Gynecology and Obstetrics · 2015 · vol. 292(5) , pp. 1075–1081 · doi:10.1007/s00404-015-3695-0 · PMID:25894338 · W2085504852
article OA: closed CC0
AI-generated summary by claude@2026-06+body, 2026-06-12

AK000953 silencing enhanced danazol's efficacy in inhibiting uterine fibroid cell proliferation, inducing apoptosis, and reducing invasion in vitro and in vivo.

One-sentence paraphrase of the abstract; not a substitute for reading it. No clinical advice. How this works

AI-generated deep summary by claude@2026-06, 2026-06-12 · read from full text

The paper studied whether silencing of AK000953 could enhance the effects of danazol on uterine fibroids, using uterine fibroid tissue versus normal uterine tissue. Differential AK000953 expression was assessed by quantitative PCR, followed by in vitro experiments in cultured uterine fibroid cells where AK000953 siRNA and danazol (alone or combined) were tested for effects on cell proliferation, apoptosis, and invasion. AK000953 was reported as highly expressed in fibroid tissue, and AK000953 silencing increased danazol’s impact, with a higher inhibition rate and apoptosis rate and a lower invasion rate in the danazol–siRNA group; a guinea pig uterine fibroid model further confirmed reduced fibroid development with danazol plus AK000953 siRNA in vivo. This paper does not explicitly discuss endometriosis or adenomyosis; it was included in the corpus via a keyword match in the upstream search index.

Read from the paper's body, not the abstract. Not a substitute for reading the paper. No clinical advice. How this works

Abstract

PurposeOur aim was to study the role of AK000953 silencing for the killing effect of danazol on uterine fibroids.MethodsQuantitative PCR was applied to identify differential expression of AK000953 in uterine fibroid tissue and normal uterine tissue. Then we isolated and cultured uterine fibroid cells, designed the siRNA of AK000953 to silence its expression in uterine fibroid cells, and detected the treatment effect of danazol and AK000953 siRNA on cell proliferation, cell apoptosis, and cell invasion. Finally, guinea pig model of uterine fibroids was constructed to verify the effect of AK000953 silencing on uterine fibroid treatment with danazol in vivo.ResultsQuantitative PCR showed that the AK000953 gene was highly expressed in uterine fibroid tissue compared with normal uterine tissue (2.1 ± 0.15 vs. 0.8 ± 0.05, p < 0.01). After AK000953 silencing in uterine fibroid cells, we discovered that the inhibition rate in danazol-siRNA group was 56 ± 5 %, the cell apoptosis rate of danazol-siRNA group was 43 ± 2.3 %, and the invasion rate of uterine fibroid cells was 12 ± 1 %, which all showed significant differences with the control group or danazol group. Guinea pig model confirmed that the treatment of danazol and AK000953 siRNA effectively inhibited the development of fibroids in vivo.ConclusionAK000953 silencing could effectively enhance the killing effect of danazol on uterine fibroid cells.
Full text 6,191 characters · extracted from oa-doi-fallback · 5 sections · click to expand

Abstract

Purpose Our aim was to study the role of AK000953 silencing for the killing effect of danazol on uterine fibroids.

Methods

Quantitative PCR was applied to identify differential expression of AK000953 in uterine fibroid tissue and normal uterine tissue. Then we isolated and cultured uterine fibroid cells, designed the siRNA of AK000953 to silence its expression in uterine fibroid cells, and detected the treatment effect of danazol and AK000953 siRNA on cell proliferation, cell apoptosis, and cell invasion. Finally, guinea pig model of uterine fibroids was constructed to verify the effect of AK000953 silencing on uterine fibroid treatment with danazol in vivo.

Results

Quantitative PCR showed that the AK000953 gene was highly expressed in uterine fibroid tissue compared with normal uterine tissue (2.1 ± 0.15 vs. 0.8 ± 0.05, p < 0.01). After AK000953 silencing in uterine fibroid cells, we discovered that the inhibition rate in danazol-siRNA group was 56 ± 5 %, the cell apoptosis rate of danazol-siRNA group was 43 ± 2.3 %, and the invasion rate of uterine fibroid cells was 12 ± 1 %, which all showed significant differences with the control group or danazol group. Guinea pig model confirmed that the treatment of danazol and AK000953 siRNA effectively inhibited the development of fibroids in vivo.

Conclusion

AK000953 silencing could effectively enhance the killing effect of danazol on uterine fibroid cells. Similar content being viewed by others

References

Stewart EA (2001) Uterine fibroids. Lancet 357(9252):293–298 Rabinovici J, David M, Fukunishi H, Morita Y, Gostout BS, Stewart EA (2010) Pregnancy outcome after magnetic resonance–guided focused ultrasound surgery (MRgFUS) for conservative treatment of uterine fibroids. Fertil Steril 93(1):199–209 Lethaby A, Vollenhoven B, Sowter M (2011) Pre-operative GnRH analogue therapy before hysterectomy or myomectomy for uterine fibroids (review) Pron G, Bennett J, Common A, Wall J, Asch M, Sniderman K (2003) The Ontario Uterine Fibroid Embolization Trial. Part 2. Uterine fibroid reduction and symptom relief after uterine artery embolization for fibroids. Fertil Steril 79(1):120–127 Edwards RD, Moss JG, Lumsden MA, Wu O, Murray LS, Twaddle S, Murray GD (2007) Uterine-artery embolization versus surgery for symptomatic uterine fibroids. N Engl J Med 356(4):360–370 Sankaran S, Manyonda IT (2008) Medical management of fibroids. Best Pract Res Clin Obstet Gynaecol 22(4):655–676 De Leo V, Morgante G, La Marca A, Musacchio MC, Sorace M, Cavicchioli C, Petraglia F (2002) A benefit-risk assessment of medical treatment for uterine leiomyomas. Drug Saf 25(11):759–779 Katula KS, Heinloth AN, Paules RS (2007) Folate deficiency in normal human fibroblasts leads to altered expression of genes primarily linked to cell signaling, the cytoskeleton and extracellular matrix. J Nutr Biochem 18(8):541–552 Tan FK, Hildebrand BA, Lester MS, Stivers DN, Pounds S, Zhou X, Wallis DD, Milewicz DM, Reveille JD, Mayes MD (2005) Classification analysis of the transcriptosome of nonlesional cultured dermal fibroblasts from systemic sclerosis patients with early disease. Arthritis Rheum 52(3):865–876 Zhong H, Simons JW (1999) Direct comparison of GAPDH, β-actin, cyclophilin, and 28S rRNA as internal standards for quantifying RNA levels under hypoxia. Biochem Biophys Res Commun 259(3):523–526 Porter KB, Tsibris J, Nicosia SV, Murphy JM, O’Brien WF, Rao PS, Spellacy WN (1995) Estrogen-induced guinea pig model for uterine leiomyomas: do the ovaries protect? Biol Reprod 52(4):824–832 Landen CN, Chavez-Reyes A, Bucana C, Schmandt R, Deavers MT, Lopez-Berestein G, Sood AK (2005) Therapeutic EphA2 gene targeting in vivo using neutral liposomal small interfering RNA delivery. Cancer Res 65(15):6910–6918 Nieman LK, Blocker W, Nansel T, Mahoney S, Reynolds J, Blithe D, Wesley R, Armstrong A (2011) Efficacy and tolerability of CDB-2914 treatment for symptomatic uterine fibroids: a randomized, double-blind, placebo-controlled, phase IIb study. Fertil Steril 95(2):767–772.e762 Lu D, Song H, Shi G (2013) Anti-TNF-α treatment for pelvic pain associated with endometriosis. Cochrane Database Syst Rev 3:CD008088 Cui J, Shi Y, Zhou H, Li J (2004) The changes of gene expression profiles in hydatidiform mole and choriocarcinoma with hyperplasia of trophoblasts. Int J Gynecol Cancer 14(5):984–997 Velazquez I, Alter BP (2004) Androgens and liver tumors: Fanconi’s anemia and non-Fanconi’s conditions. Am J Hematol 77(3):257–267 Barbieri RL, Ryan KJ (1981) Danazol: endocrine pharmacology and therapeutic applications. Am J Obstet Gynecol 141(4):453–463 Maruo T, Matsuo H, Shimomura Y, Kurachi O, Gao Z, Nakago S, Yamada T, Chen W, Wang J (2003) Effects of progesterone on growth factor expression in human uterine leiomyoma. Steroids 68(10):817–824 Zhao Y, Wen Y, Polan ML, Qiao J, Chen BH (2007) Increased expression of latent TGF-ß binding protein-1 and fibrillin-1 in human uterine leiomyomata. Mol Hum Reprod 13(5):343–349 Dowsett M, Allred C, Knox J, Quinn E, Salter J, Wale C, Cuzick J, Houghton J, Williams N, Mallon E (2008) Relationship between quantitative estrogen and progesterone receptor expression and human epidermal growth factor receptor 2 (HER-2) status with recurrence in the Arimidex, Tamoxifen, Alone or in Combination trial. J Clin Oncol 26(7):1059–1065 Acknowledgments This study was supported by grants from the National Natural Science Foundation of China (No. 81302243), Lanzhou military region subject (No. CLZ13JB21, CLZ14JA11), Shannxi National Science Foundation (No. 2014JM4157). Conflict of interest The Authors declare that they have no conflicts of interest to disclose. Author information Authors and Affiliations Corresponding author Additional information S. Li and L. Niu contributed equally to this work and are co-first authors. Rights and permissions About this article Cite this article Li, S., Zhang, Y., Niu, L. et al. AK000953 silencing can enhance the killing effect of danazol on uterine fibroids. Arch Gynecol Obstet 292, 1075–1081 (2015). https://doi.org/10.1007/s00404-015-3695-0 Received: Accepted: Published: Issue date: DOI: https://doi.org/10.1007/s00404-015-3695-0

Text is read by the "Ask this paper" AI Q&A widget below. Extraction quality varies by source — PMC NXML preserves structure cleanly, OA-HTML may include some navigation residue, and OA-PDF can have broken hyphenation. The publisher copy (via DOI) is the canonical version.

My notes (saved in your browser only)

Ask this paper AI returns verbatim quotes from the full text · source: oa-doi-fallback

Answers must be backed by verbatim quotes from this paper's full text. Hallucinated quotes are dropped automatically; if no verbatim passage answers the question, we say so. How this works

Citation neighborhood (sparse)

Too few in-corpus citations on either side for a chart; here are the lists.

Cites (3)

References (20)

Source provenance

openalex
last seen: 2026-05-11T06:14:16.517584+00:00
License: CC0 · commercial use OK