Inhibiting the PI3K/Akt pathway reversed progestin resistance in endometrial cancer.
Cancer Sci
; 102(3): 557-64, 2011 Mar.
Article
em En
| MEDLINE
| ID: mdl-21205080
ABSTRACT
Progestin resistance is the main obstacle to successful conservative therapy in young endometrial cancer patients. To investigate the molecular events that lead to progestin resistance and to find a possible way to reverse progestin resistance in endometrial cancer, we established a progestin-resistant Ishikawa cell line by long-term progestin treatment to downregulate progesterone receptor (PR) expression. Both medoxyprogesterone acetate (MPA) and LY294002, a phosphatidylinositol 3-kinase (PI3K) inhibitor, were assayed for their effects on the proliferation of progestin-sensitive and progestin-resistant cancer cells, respectively. The MPA inhibited the PI3K/Akt pathway and suppressed cell proliferation in progestin-sensitive Ishikawa cells, but activated the PI3K/Akt pathway and had no effect on cell proliferation in progestin-resistant Ishikawa cells or HEC-1A cells. Inhibiting the PI3K/Akt pathway by LY294002 upregulated PR expression and diminished cell growth, especially in progestin-resistant endometrial cancer cells. In vivo endometrial cancer xenograft studies in nude mice also showed that inhibiting the PI3K/Akt pathway reversed progestin resistance in endometrial cancer. Our results indicate that activation of the PI3K/Akt pathway by progestin without PR mediation plays an important role in progestin resistance to endometrial cancer cells. In addition, inhibiting the PI3K/Akt pathway might reverse progestin resistance in endometrial cancer.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
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Morfolinas
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Cromonas
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Neoplasias do Endométrio
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Acetato de Medroxiprogesterona
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Antineoplásicos Hormonais
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Proteínas Proto-Oncogênicas c-akt
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Inibidores de Fosfoinositídeo-3 Quinase
Limite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Cancer Sci
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
China