The effectiveness of nano chemotherapeutic particles combined with mifepristone depends on the PR isoform ratio in preclinical models of breast cancer

Sequeira, Gonzalo R.; Vanzulli, Silvia I.; Rojas, Paulina S.; Lamb, Caroline A.; Colombo, Lucas L.; May, María; Molinolo, Alfredo A.; Lanari, Claudia

doi:10.18632/oncotarget.1922

Cited by 18 publications

(23 citation statements)

References 45 publications

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“…2009 ). The response of these tumors to mifepristone is associated with an increase in tumor stroma and microvasculature, which allows better access to other chemotherapeutic agents such as paclitaxel or doxorubicin when provided in nanoparticle formulations, leading to a better therapeutic outcome (i.e., further growth inhibition than that caused by paclitaxel or doxorubicin alone) ( Sequeira et al . 2014 ).…”

Section: Breast Cancermentioning

confidence: 99%

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Antiprogestins in gynecological diseases

Goyeneche

Telleria

2015

Reproduction

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Antiprogestins constitute a group of compounds, developed since the early 1980s, that bind progesterone receptors (PR) with different affinities. The first clinical uses for antiprogestins were in reproductive medicine: e.g. menstrual regulation, emergency contraception, and termination of early pregnancies. These initial applications, however, belied the capacity for these compounds to interfere with cell growth. Within the context of gynaecological diseases, antiprogestins can block the growth of and kill gynaecological-related cancer cells, such as those originating in the breast, ovary, endometrium, and cervix. They also can interrupt the excessive growth of cells giving rise to benign gynaecological diseases such as endometriosis and leiomyomata (uterine fibroids). In this article, we present a review of the literature providing support for the anti-growth activity antiprogestins command over cells from various gynaecological diseases. We also provide a summary of the cellular and molecular mechanisms reported for these compounds that lead to cell growth-inhibition and death. The preclinical knowledge gained during the past few years provides robust evidence to encourage using antiprogestins in order to alleviate the burden of gynaecological diseases, either as monotherapies or as adjuvants of other therapies with the perspective of allowing for long-term treatments with tolerable side effects. The key to the clinical success of antiprogestins in this field, likely lies in selecting those patients who will benefit from this therapy. This can be achieved by defining the genetic makeup required—within each particular gynaecological disease—for attaining an objective response to antiprogestin-driven growth-inhibition therapy.

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Section: Breast Cancermentioning

confidence: 99%

“…1999 ). More recently, it has been demonstrated that in these cells the antiprogestin increased tissue remodeling, which favored the efficacy of nanoparticle carrying chemotherapeutic agents ( Sequeira et al . 2014 ).…”

Section: Mechanisms Of Growth Inhibition Driven By Antiprogestinsmentioning

confidence: 99%

Antiprogestins in gynecological diseases

Goyeneche

Telleria

2015

Reproduction

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“…It provides a unique approach and comprehensive technology against cancer because of the special optical, magnetic, or structural properties of the nanometer-sized particles [15-19]. Our group has demonstrated that 20 nm gold nanoparticles (AuNPs) inhibited proliferation, angiogenesis and metastases in a preclinical mouse model of ovarian cancer [12,20,21].…”

Section: Introductionmentioning

confidence: 99%

Sensitization of ovarian cancer cells to cisplatin by gold nanoparticles

et al. 2014

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Recently we reported that gold nanoparticles (AuNPs) inhibit ovarian tumor growth and metastasis in mice by reversing epithelial-mesenchymal transition (EMT). Since EMT is known to confer drug resistance to cancer cells, we wanted to investigate whether anti-EMT property of AuNP could be utilized to sensitize ovarian cancer cells to cisplatin. Herein, we report that AuNPs prevent cisplatin-induced acquired chemoresistance and stemness in ovarian cancer cells and sensitize them to cisplatin. AuNPs inhibit cisplatin induced EMT, decrease the side population cells and key stem cell markers such as ALDH1, CD44, CD133, Sox2, MDR1 and ABCG2 in ovarian cancer cells. Mechanistically, AuNPs prevent cisplatin-induced activation of Akt and NF-κB signaling axis in ovarian cancer cells that are critical for EMT, stem cell maintenance and drug resistance. In vivo, AuNPs sensitize orthotopically implanted ovarian tumor to a low dose of cisplatin and significantly inhibit tumor growth via facilitated delivery of both AuNP and cisplatin. These findings suggest that by depleting stem cell pools and inhibiting key molecular pathways gold nanoparticles sensitize ovarian cancer cells to cisplatin and may be used in combination to inhibit tumor growth and metastasis in ovarian cancer.

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“…Similarly, metapristone (RU42633) is the primary metabolite of mifepristone (RU486) [14], which is used to terminate pregnancy in the rst month in clinic [15]. Some reports had showed that metapristone could inhibit lots of cancer cell proliferation [16,17]. However, there were few reports that indicated that whether metapristone could treat endometrial cancer.…”

Section: Introductionmentioning

confidence: 99%

Metapristone (RU486 derivative) inhibits endometrial cancer cell progress through regulating miR-492/Klf5/Nrf1 axis

Chang

Hao

Jia

et al. 2020

Preprint

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Background: Endometrial cancer is the prevalent invasive gynecological cancer in the world. The pathogenesis of endometrial cancer involves many signaling pathways which are related with transcription factors or microRNAs. Metapristone is a hormone related drug and widely used in endometrial cancer clinical therapeutics. However, the deep regulatory mechanism of metapristone is not clear. In this research, we aimed to figure out the specific molecular mechanism during the treatment of endometrial cancer with metapristone.Methods: In this study, RL95-2 cells and Ishikawa cells were used as the endometrial cancer cell models. miR-492 was transfected into RL95-2 cells and Ishikawa cells. The miRNA expression was measured by qRT-PCR. Moreover, the mice tumor model was used to confirm the function of metapristone and the regulating process by miR-492/Klf5/Nrf1 axis in vivo. The protein expression was measured by western blot. Cell proliferation and apoptosis was monitored using the MTT assay, cell colony formation assay and EdU assay.Results: Firstly, the results indicated that metapristone as a kind of hormone-related drugs could significantly inhibit the endometrial cancer cell growth through regulating cell apoptosis-related gene expression. Meanwhile, miR-492 was detected to be highly expressed in the endometrial cancer cell lines. Overexpression of miR-492 could promote the cell proliferation and inhibit the cell apoptosis. Furthermore, the results demonstrated that the downstream target genes of miR-492 were Klf5 and Nrf1, which were inhibited by metapristone. At the animal level, metapristone also inhibited the endometrial cancer cell growth through down-regulating the expression of miR-492 and decreasing the protein level of Klf5 and Nrf1. Conclusion: Taken together, this study indicated that metapristone inhibited the endometrial cancer cell growth through regulating the cell apoptosis related signaling pathway and the expression of miR-492 and its downstream target genes (Klf5 and Nrf1), which provided the theoretical basis of endometrial cancer in clinical treatment.

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The effectiveness of nano chemotherapeutic particles combined with mifepristone depends on the PR isoform ratio in preclinical models of breast cancer

Cited by 18 publications

References 45 publications

Antiprogestins in gynecological diseases

Antiprogestins in gynecological diseases

Sensitization of ovarian cancer cells to cisplatin by gold nanoparticles

Metapristone (RU486 derivative) inhibits endometrial cancer cell progress through regulating miR-492/Klf5/Nrf1 axis

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