The effectiveness of an anti-human IL-6 receptor monoclonal antibody combined with chemotherapy to target colon cancer stem-like cells

摘要: Recent studies have demonstrated that cancer stem cells (CSCs) can initiate and sustain tumor growth exhibit resistance to clinical cytotoxic therapies. Therefore, CSCs represent the main target of anticancer therapy. Interleukin-6 (IL-6) promotes cellular proliferation drug in colorectal cancer, its serum levels correlate with patient survival. IL-6 downstream signaling molecule signal transducer activator transcription-3 (STAT3) potential molecular targets. In present study, we investigated effects components on cell biology, particularly chemoresistance CSCs, explore targets for The colon line WiDr was cultured serum-free, non-adherent, three-dimensional spheroid-forming conditions enrich cell-like population. Spheroid-forming slowly proliferated expressed high Oct-4, Klf4, Bmi-1, Lgr5, IL-6, Notch 3 compared adherent cells. Treatment an anti-human receptor monoclonal antibody reduced spheroid formation, cell-related gene expression, 5-fluorouracil (5-FU) resistance. addition, treatment enhanced p-STAT3 (Tyr705), expression 3, 5-FU. siRNA targeting suppressed Oct-4 Lgr5 5-FU chemoresistance, whereas STAT3 inhibition along growth. Taken together, these results indicate functions dichotomous pathways involving induction activation. former pathway is involved stem-like biology latter leads accelerated chemoresistance. Thus, or may be superior CSC-targeting therapies concomitant drugs.