Mifepristone has limited activity to enhance the in vivo efficacy of docetaxel and enzalutamide against bone metastatic and castration-resistant prostate cancer

Yang Yang, Xin Li, Kenza Mamouni, Omer Kucuk, Daqing Wu

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Background: Mifepristone has gained great interest in its potential as a novel agent against human cancers, including prostate cancer (PCA). However, recent clinical trials using mifepristone in PCA and other cancers have been disappointing. We evaluated the in vitro and in vivo activities of mifepristone, in combination with docetaxel and enzalutamide, against bone metastatic castration-resistant PCA. Materials and Methods: The effects of mifepristone, alone or in combination with docetaxel or enzalutamide, on PCA cell viability, in vitro, were determined by the colorimetric assay. Intratibial model of C4-2-Luc tumors in athymic nude mice was used to evaluate the in vivo efficacy of mifepristone alone or in combination with docetaxel or enzalutamide. Tumor growth in mouse bone was assessed by serum prostate-specific antigen (PSA) levels and radiography. Results: Although mifepristone exhibits a certain degree of synergism with docetaxel or enzalutamide in cell culture, statistical analyses showed that combination regimens fail to demonstrate effectiveness in suppressing the skeletal growth of PCA and enhancing the in vivo efficacy of docetaxel or enzalutamide in athymic nude mice (p>0.05). Conclusion: These results provide the first pre-clinical evidence suggesting that mifepristone may not effectively inhibit bone metastatic PCA, either as a single agent or combined with standard chemotherapy and androgen-deprivation therapy. This report may raise concerns over the clinical use of mifepristone in the management of advanced PCA.

Original languageEnglish (US)
Pages (from-to)6235-6243
Number of pages9
JournalAnticancer research
Volume37
Issue number11
DOIs
StatePublished - Nov 2017

Fingerprint

docetaxel
Mifepristone
Castration
Prostatic Neoplasms
Bone and Bones
Nude Mice
Neoplasms
MDV 3100
Prostate-Specific Antigen
Growth
Radiography
Androgens

Keywords

  • Bone metastasis
  • Castration-resistant prostate cancer
  • Docetaxel
  • Enzalutamide
  • Mifepristone

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Mifepristone has limited activity to enhance the in vivo efficacy of docetaxel and enzalutamide against bone metastatic and castration-resistant prostate cancer. / Yang, Yang; Li, Xin; Mamouni, Kenza; Kucuk, Omer; Wu, Daqing.

In: Anticancer research, Vol. 37, No. 11, 11.2017, p. 6235-6243.

Research output: Contribution to journalArticle

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abstract = "Background: Mifepristone has gained great interest in its potential as a novel agent against human cancers, including prostate cancer (PCA). However, recent clinical trials using mifepristone in PCA and other cancers have been disappointing. We evaluated the in vitro and in vivo activities of mifepristone, in combination with docetaxel and enzalutamide, against bone metastatic castration-resistant PCA. Materials and Methods: The effects of mifepristone, alone or in combination with docetaxel or enzalutamide, on PCA cell viability, in vitro, were determined by the colorimetric assay. Intratibial model of C4-2-Luc tumors in athymic nude mice was used to evaluate the in vivo efficacy of mifepristone alone or in combination with docetaxel or enzalutamide. Tumor growth in mouse bone was assessed by serum prostate-specific antigen (PSA) levels and radiography. Results: Although mifepristone exhibits a certain degree of synergism with docetaxel or enzalutamide in cell culture, statistical analyses showed that combination regimens fail to demonstrate effectiveness in suppressing the skeletal growth of PCA and enhancing the in vivo efficacy of docetaxel or enzalutamide in athymic nude mice (p>0.05). Conclusion: These results provide the first pre-clinical evidence suggesting that mifepristone may not effectively inhibit bone metastatic PCA, either as a single agent or combined with standard chemotherapy and androgen-deprivation therapy. This report may raise concerns over the clinical use of mifepristone in the management of advanced PCA.",
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T1 - Mifepristone has limited activity to enhance the in vivo efficacy of docetaxel and enzalutamide against bone metastatic and castration-resistant prostate cancer

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AU - Wu, Daqing

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N2 - Background: Mifepristone has gained great interest in its potential as a novel agent against human cancers, including prostate cancer (PCA). However, recent clinical trials using mifepristone in PCA and other cancers have been disappointing. We evaluated the in vitro and in vivo activities of mifepristone, in combination with docetaxel and enzalutamide, against bone metastatic castration-resistant PCA. Materials and Methods: The effects of mifepristone, alone or in combination with docetaxel or enzalutamide, on PCA cell viability, in vitro, were determined by the colorimetric assay. Intratibial model of C4-2-Luc tumors in athymic nude mice was used to evaluate the in vivo efficacy of mifepristone alone or in combination with docetaxel or enzalutamide. Tumor growth in mouse bone was assessed by serum prostate-specific antigen (PSA) levels and radiography. Results: Although mifepristone exhibits a certain degree of synergism with docetaxel or enzalutamide in cell culture, statistical analyses showed that combination regimens fail to demonstrate effectiveness in suppressing the skeletal growth of PCA and enhancing the in vivo efficacy of docetaxel or enzalutamide in athymic nude mice (p>0.05). Conclusion: These results provide the first pre-clinical evidence suggesting that mifepristone may not effectively inhibit bone metastatic PCA, either as a single agent or combined with standard chemotherapy and androgen-deprivation therapy. This report may raise concerns over the clinical use of mifepristone in the management of advanced PCA.

AB - Background: Mifepristone has gained great interest in its potential as a novel agent against human cancers, including prostate cancer (PCA). However, recent clinical trials using mifepristone in PCA and other cancers have been disappointing. We evaluated the in vitro and in vivo activities of mifepristone, in combination with docetaxel and enzalutamide, against bone metastatic castration-resistant PCA. Materials and Methods: The effects of mifepristone, alone or in combination with docetaxel or enzalutamide, on PCA cell viability, in vitro, were determined by the colorimetric assay. Intratibial model of C4-2-Luc tumors in athymic nude mice was used to evaluate the in vivo efficacy of mifepristone alone or in combination with docetaxel or enzalutamide. Tumor growth in mouse bone was assessed by serum prostate-specific antigen (PSA) levels and radiography. Results: Although mifepristone exhibits a certain degree of synergism with docetaxel or enzalutamide in cell culture, statistical analyses showed that combination regimens fail to demonstrate effectiveness in suppressing the skeletal growth of PCA and enhancing the in vivo efficacy of docetaxel or enzalutamide in athymic nude mice (p>0.05). Conclusion: These results provide the first pre-clinical evidence suggesting that mifepristone may not effectively inhibit bone metastatic PCA, either as a single agent or combined with standard chemotherapy and androgen-deprivation therapy. This report may raise concerns over the clinical use of mifepristone in the management of advanced PCA.

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