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Drug resistance largely limits the efficacy and efficiency of chemotherapeutics, which is a first-line treatment for liver cancer, consequently triggering a complete failure in clinical application. There are numerous attempts in exploring potential strategies for avoiding drug resistance, but none of them has effectively addressed this problem. Therefore, novel molecular targets and agents proposed for addressing drug resistance are needed. This study established 5-fluorouracil (5-Fu)-resistant HepG2 cells (HepG2/R) and showed that a FOXM1-targeted peptide, P201, reactivated 5-Fu to attenuate HepG2/R cell viability, proliferation, migration and promote apoptosis. Moreover, both pharmacological studies and RNA genomic sequencing results uncovered that combination of P201 and 5-Fu notably decreased expressions of FOXM1, MDR1 and ABCG2 compared to 5-Fu alone, indicating P201 overcame 5-Fu resistance mainly through inhibiting FOXM1 and ABC transporters. Therefore, P201 could inhibit ABC transporters by targeting FOXM1 in HepG-2/R cells, overcoming 5-Fu resistance and enhancing anti-cancer drug sensitivity. FOXM1 may be a new target for overcoming 5-Fu resistance in HepG2 cell while the combination treatment of P201 and 5-Fu may serve as a potential strategy for treating liver cancer.
相似文献In the paper, resonances of different waveguide structures with various vertical indirect coupled cavities were investigated by FDTD (finite difference-time domain). In the silicon cavity, Fano resonance could be observed at about 1430 nm. The coupling distance for the gold cavity/air cavity had less effect on the transmittance of the main waveguide but had a great influence on the transmission for water cavity in the visible region, which showed that water cavity could adjust resonance of waveguide structures. In addition, with the increment of refractive index n, the resonance peak at about 850 nm moved to the long wavelength (redshift). Dispersion rate about 2 × 10–3/nm indicated that the transparent dielectric selectively absorbed the surface plasmon polariton wave and the sensitivity of the waveguide structure designed in this paper has high stability for the refractive index of the main waveguide cavity. Obvious Fano resonance could be observed with the increase of refractive index for silicon cavity. Among the four dielectrics, silicon and water are suitable for studying Fano resonance and filter dielectrics.
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