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Objective To investigate the effect of CD147 monoclonal antibody (mAb) on the natural resistance to paclitaxel (TAX) in the human cervical cancer line (HCE1) multicellular spheroid (HCE1/MCS) model and if CD147 mAb can reverse the HCE1/MCS resistance to TAX. Methods HCE1/MCS was obtained by liquid overlay and rotating technique. HCE1/MCS morphological changes were observed before or after the interference of CD147 mAb. The effects of TAX on HCE1/MCS (including inhibition ratio, IC50 and index of multicellular resistance) before or after CD147 mAb treatment were determined by the method of WST-1 and the inhibition ratio curve was mapped. Cell cycle and apoptosis were detected by flow cytometer (FCM). The expression of CD147 and P-gp of both HCE1/MC and HCE1/MCS was detected by immunocytochemistry. Results HCE1/MCS was established successfully. CD147 mAb could inhibit HCE1/MCS from forming spheroids. CD147 mAb could enhance the sensitivity of HCE1/MCS to TAX. IC50 in different concentrations of CD147 mAb (5,10,20 μg/mL) HCE1/MCS group were (40.31±3.73), (32.43±1.56), and (30.69±1.01) μg/mL. CD147 mAb resulted in G1/G0 arrest in HCE1/MCS. CD147 mAb of low concentrations (0-10 μg/mL) caused a dose-dependent inhibition of HCE1/MCS (P<0.05). Combined with TAX, CD147 mAb could also induce HCE1/MCS cell cycle arrest in both G1/S and G2/M stage. The expression of CD147 and P-gp was consistent in HCE1/MCS groups. Conclusion CD147 plays an important role in muliticellular resistance of cervical cancer and inhibition of CD147 can synergistically reverse the multicellular drug resistance (MCR) in cervical cancer. The MCR of HCE1/MCS mediated by CD147 is related to P-gp.
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Background and purpose:TrkB,a neurotrophic tyrosine kinase receptor,serves as a potent and specific suppressor of anoikis of non-malignant epithelial cells,and induces high invasion capacity in these cells.TrkB over-expression has been associated with chemotherapy resistance and poor survival in neuroblastoma and some other highly aggressive cancers.However,the relationship of the expression of TrkB to anoikis resistance in ovarian cancer cells has rarely been reported in literature.This study investigated the expression and significance of anoikis- suppressor TrkB in OVCAR-3 ovarian cancer cells.Methods:The expression of TrkB and its ligand BDNF was evaluated in OVCAR-3 ovarian cancer cells under different culture conditions by RT-PCR and Western blot.Results: TrkB mRNA was overexpressed in multicellular spheroids(cell-spheroids,anchorage-independent culture,AIC)as compared to that in OVCAR-3 cells(adhesive-cells,adhesive culture,AC),(35.3?0.7)% versus(23.5?0.5)%;but BDNF mRNA expression was the opposite to the above situation,(41.4?0.6)% versus(32.24?0.7)%(P