Human ovarian cancer stem/progenitor cells are stimulated by doxorubicin but inhibited by Mullerian inhibiting substance

摘要: Women with late-stage ovarian cancer usually develop chemotherapeutic-resistant recurrence. It has been theorized that a rare stem cell, which is responsible for the growth and maintenance of tumor, also resistant to conventional chemotherapeutics. We have isolated from multiple cell lines an cell-enriched population marked by CD44, CD24, Epcam (3+) negative selection Ecadherin (Ecad−) comprises less than 1% cells increased colony formation shorter tumor-free intervals in vivo after limiting dilution. Surprisingly, these are not only chemotherapeutics such as doxorubicin, but stimulated it, evidenced significantly number colonies treated 3+Ecad− cells. Similarly, proliferation monolayer treatment, either doxorubicin or cisplatin, compared unseparated cell-depleted 3−Ecad+ However, sensitive Mullerian inhibiting substance (MIS), decreased formation. MIS inhibits inducing G1 arrest subpopulation through induction cyclin-dependent kinase inhibitors. selectively expressed LIN28, colocalized immunofluorescence 3+ markers human carcinoma line, OVCAR-5, highly transgenic murine models other lines. These results suggest may be stimulative selective inhibition treating targeting LIN28 should considered development therapeutics.