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  • Title: Knock-down of P-glycoprotein reverses taxol resistance in ovarian cancer multicellular spheroids.
    Author: Xing H, Wang S, Weng D, Chen G, Yang X, Zhou J, Xu G, Lu Y, Ma D.
    Journal: Oncol Rep; 2007 Jan; 17(1):117-22. PubMed ID: 17143487.
    Abstract:
    We previously established that multicellular ovarian cancer spheroids develop intrinsic multidrug resistance with the appearance of quiescent cell areas. p27 protein is a determinant of such resistance. However, the precise molecular basis of such resistance remains unknown. We demonstrated herein that these multicellular ovarian cancer spheroids expressed high levels of p27 and P-gp protein. Compared with monolayer cells, there is a significant increase in the resistance of spheroids cells to anticancer reagent Taxol. Antisense oligodeoxynucleotide not only mediated down-regulation of p27, but also P-gp expression in multicellular spheroids. Selective small interfering RNAs (siRNA) of P-gp with MDR1-targeted short hairpin RNAs (shRNA) expression vector sensitized the cells to Taxol. These results suggest that both p27 and P-gp can modulate Taxol sensitivity respectively, while p27 requires P-gp for its full function. Increased P-gp protein expression through p27 mediation is one of the major mechanisms of Taxol resistance in ovarian cancer multicellular spheroids.
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