Phase II Study of Mifepristone (RU486) in Refractory Ovarian Cancer

Rocereto, Thomas F.; Saul, Howard M.; Aikins, James; Paulson, James C.

doi:10.1006/gyno.2000.5789

Cited by 70 publications

(49 citation statements)

References 8 publications

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“…Interestingly, recent studies [21][22][23][24][25] have proved that mifepristone exerts markedly anticancer effects and reversal effects on MDR in some cancer cells with no serious side-effects. Thus, there is an increasing interest in exploring the reversal effect of mifepristone on MDR in human gastric cancer cells.…”

Section: Discussionmentioning

confidence: 99%

Reversal of multidrug resistance in drug-resistant human gastric cancer cell line SGC7901/VCR by antiprogestin drug mifepristone

Daqiang

Wang²,

Bai³

et al. 2004

WJG

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AIM:To explore the reversal effect of mifepristone on multidrug resistance (MDR) in drug-resistant human gastric cancer cell line SGC7901/VCR and its mechanisms. METHODS:Expression of multidrug resistance-associated protein(MRP) was detected using reverse transcriptionpolymerase chain reaction(RT-PCR). Flow cytometry was used to assay the expression of P-glycoprotein(P-gp), Bcl-2, Bax, and the mean fluorescent intensity of intracellular rhodamine 123 in the cells. Meanwhile, the protein levels of Bcl-2 and Bax were also detected by Western blotting analysis. The sensitivity of cells to the anticancer agent, vincrimycin(VCR), and the intracellular [ 3 H]VCR accumulation were determined by tetrazolium blue (MTT) assay and a liquid scintillation counter, respectively. RESULTS:Expression of MRP and P-gp in SGC7901/VCR cells was 6.04-and 8.37-fold higher as compared with its parental SGC7901 cells, respectively. After treatment with 1, 5, 10, and 20 µmol/L mifepristone, SGC7901/VCR cells showed a 1.34-, 2.29-, 3.11-, and 3.71-fold increase in the accumulation of intracellular VCR, a known substrate of MRP, and a 1.03-, 2.04-, 3.08-, and 3.68-fold increase in the retention of rhodamine 123, an indicator of P-gp function, respectively. MTT assay revealed that the resistance of SGC7901/VCR cells to VCR was 11.96-fold higher than that of its parental cells. The chemosensitivity of SGC7901/VCR cells to VCR was enhanced by 1.02-, 7.19-, 12.84-, and 21.17-fold after treatment with mifepristone at above-mentioned dose. After 96 h of incubation with mifepristone 10 µmol/L, a concentration close to plasma concentrations achievable in human, the expression of Bcl-2 protein was decreased to (9.21±0.65)% from (25.32±1.44)%, whereas the expression of Bax protein was increased to (19.69±1.13)% from (1.24±0.78)% (P<0.01). Additionally, the effects of mifepristone on the expression of Bcl-2 and Bax proteins in SGC7901/VCR cells were further demonstrated by Western blotting analysis. CONCLUSION:Mifepristone has potent reversal effect on MDR in SGC7901/VCR via inhibiting the function of MRP and P-gp, modulating the expression of Bcl-2 and Bax proteins, and enhancing the sensitivity to anticancer agent VCR.Li DQ, Wang ZB, Bai J, Zhao J, Wang Y, Hu K, Du YH. Reversal of multidrug resistance in drug-resistant human gastric cancer cell line SGC7901/VCR by antiprogestin drug mifepristone.

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Section: Discussionmentioning

confidence: 99%

Reversal of multidrug resistance in drug-resistant human gastric cancer cell line SGC7901/VCR by antiprogestin drug mifepristone

Daqiang

Wang²,

Bai³

et al. 2004

WJG

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“…Given the anti-proliferative effects observed in vitro and in vivo for PRAs (Freeburg et al, 2009b;Goyeneche et al, 2007;Ohara et al, 2007;Poole et al, 2006;Tieszen et al, 2011), the broader utility of this class in treating other benign and malignant growth conditions has not gone unnoticed Robertson et al, 1999;Rocereto et al, 2000;Wilkens et al, 2008). In the closely related condition of uterine fibroids, small studies have demonstrated a reduction in myoma volume and uterine bleeding with asoprisnil and RU-486 (Chabbert-Buffet et al, 2005;DeManno et al, 2003;Fiscella et al, 2006).…”

Section: Clinical Evaluation In Healthy Women and Women With Endometrmentioning

confidence: 99%

Progesterone Resistance and Targeting the Progesterone Receptors: A Therapeutic Approach to Endometriosis

Pullen¹

2012

Endometriosis - Basic Concepts and Current Research Trends

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“…Mifepristone is a progesterone antagonist, more commonly known for its abortifacent properties. Rocereto et al (2000) conducted a phase II study of mifepristone in the treatment of recurrent of persistent EOC, fallopian tube, or primary peritoneal cancer. Patients with persistent or recurrent disease less than 1 year after chemotherapy were eligible, and received mifepristone 200 mg daily for 28 day cycles.…”

Section: Progesteronementioning

confidence: 99%