Erythropoietin promotes expression of survivin via STAT3 activation and reduces sensitivity to cisplatin in cervical cancer cells
Por:
Vázquez-Mellado M.J., Cortés-Ballinas L.G., Blanco-Flores I.C., Aguilar C., Vázquez-Gómez G., Rocha-Zavaleta L.
Publicada:
1 feb 2019
Resumen:
Erythropoietin (Epo) is used for the treatment of cancer-associated
anaemia. However, certain studies have identified that the
administration of Epo mediates the acquisition of resistance to
cisplatin, which is widely used to treat cervical cancer. Our group
previously reported that cervical cancer cells express Epo receptor and
that exogenous Epo induces cell proliferation and migration. However,
the effect of Epo on cervical cancer cell death mediated by
chemotherapeutic agents has not yet been evaluated. Thus, the aim of the
present study was to assess the potential effect of Epo on the cytotoxic
activity of cisplatin in cervical cancer cells. The effect of Epo was
assessed in 3 cervical cancer-derived cell lines. It was observed that
pre-incubation with Epo induced a significant reduction of
cisplatin-induced apoptosis in vitro and in vivo. Incubation with Epo
induced the expression and activation of the transcriptional factor
signal transducer and activator of transcription 3 (STAT3), which in
turn stimulated the expression and activation of the anti-apoptotic
protein survivin. The cytotoxicity of cisplatin was partially restored
by treating the cells with MY155, an inhibitor of survivin. Conversely,
inhibition of STAT3 activation using sub-lethal doses of WP1066,
completely abolished the cytoprotective effect of Epo. These
observations indicated that Epo was able to hinder the cytotoxic effect
of cisplatin in cervical cancer cells by activating anti-apoptotic
responses regulated by STAT3.
Filiaciones:
Vázquez-Mellado M.J.:
Departamento de Biología Molecular y Biotecnología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Ciudad Universitaria, Biología Molecular y Biotecnología, Circuito Escolar S/N, Coyoacán, Ciudad de México, 04510, Mexico
Cortés-Ballinas L.G.:
Departamento de Biología Molecular y Biotecnología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Ciudad Universitaria, Biología Molecular y Biotecnología, Circuito Escolar S/N, Coyoacán, Ciudad de México, 04510, Mexico
Blanco-Flores I.C.:
Departamento de Biología Molecular y Biotecnología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Ciudad Universitaria, Biología Molecular y Biotecnología, Circuito Escolar S/N, Coyoacán, Ciudad de México, 04510, Mexico
Aguilar C.:
Departamento de Biología Molecular y Biotecnología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Ciudad Universitaria, Biología Molecular y Biotecnología, Circuito Escolar S/N, Coyoacán, Ciudad de México, 04510, Mexico
Vázquez-Gómez G.:
Medicina Genómica y Toxicología Ambiental, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Ciudad Universitaria, Circuito Escolar S/N, Coyoacán, Ciudad de México, 04510, Mexico
Rocha-Zavaleta L.:
Departamento de Biología Molecular y Biotecnología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Ciudad Universitaria, Biología Molecular y Biotecnología, Circuito Escolar S/N, Coyoacán, Ciudad de México, 04510, Mexico
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