Fig. 6. YQ-0629 targets HIF-2α to suppress stem trait of BCSCs and synergy the sensitization to PTX in vitro.

A The chemical structure of YQ-0629 and docking conformation showed the interaction of the YQ-0629 with the active site of HIF-2α through MOE software (left). YQ-0629 and HIF-2α PAS-B domain was confirmed direct binding by surface plasmon resonance (SPR)-based Biacore assay (right). B The expression level of HIF-2α was detected in the nucleus (N) and cytoplasm (C) of MCF7 MS cells cultured with YQ-0629 (10 µM) alone, PTX (3 nM) alone, or YQ-0629 (10 µM) combined with PTX (3 nM) for 72 h. C The expression and location of HIF-2α were detected in MCF7 MS cells cultured with YQ-0629 (10 µM) alone, PTX (3 nM) alone, or YQ-0629 (10 µM) combined with PTX (3 nM) for 72 h by immunofluorescence staining. Scale bar, 10 μm. D The cell viability rate of MCF7 MS cells cultured with different concentrations of YQ-0629 for 24–96 hours were determined by CCK-8 assay (left). The IC₅₀ values of PTX and synergic index (R) were calculated in MCF7 MS cells cultured with indicated dose of YQ-0629 for 72 h (right). n = 3. Student’s t test. E The self-renewal ability was detected in MCF7 MS cells cultured with YQ-0629 (10 µM) alone, PTX (3 nM) alone, or YQ-0629 (10 µM) combined with PTX (3 nM) for 72 h. n = 3. Synergic index (R). Two-way ANOVA test. Scale bar, 250 μm. F–H The mRNA expression of SOD2 and mtROS level, the expressions level of PDI, GRP78, and P-gp were detected in the MCF7 MS cells cultured with indicated dose of PTX and YQ-0629 for 72 h. n = 3. Two-way ANOVA test. **P < 0.01, **P < 0.01, ***P < 0.001, compared to MCF7 MS cells/MCF7 MS cells + PTX treatment.