Research Summary: Enhancing Chemotherapy Response with Bmi-1 Silencing in Ovarian Cancer


Undoubtedly ovarian cancer is a vexing, incurable disease for patients with
recurrent cancer and therapeutic options are limited. Although the polycomb
group gene, Bmi-1 that regulates the self-renewal of normal
stem and progenitor cells has been implicated in the pathogenesis of many human
malignancies, yet a role for Bmi-1 in influencing chemotherapy response has not
been addressed before. Here we demonstrate that silencing Bmi-1 reduces
intracellular GSH levels and thereby sensitizes chemoresistant ovarian cancer
cells to chemotherapeutics such as cisplatin. By exacerbating ROS production in
response to cisplatin, Bmi-1 silencing activates the DNA damage response
pathway, caspases and cleaves PARP resulting in the induction apoptosis in
ovarian cancer cells. In an in vivo orthotopic mouse model of
chemoresistant ovarian cancer, knockdown of Bmi-1 by nanoliposomal delivery
significantly inhibits tumor growth. While cisplatin monotherapy was inactive,
combination of Bmi-1 silencing along with cisplatin almost completely abrogated
ovarian tumor growth. Collectively these findings establish Bmi-1 as an
important new target for therapy in chemoresistant ovarian cancer.


Publisher: Public Library of Science

Date Published: 21-March-2011

Author(s): Wang E., Bhattacharyya S., Szabolcs A., Rodriguez-Aguayo C., Jennings N., Lopez-Berestein G., Mukherjee P., Sood A., Bhattacharya R.


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