title: Knock-down of P-glycoprotein reverses taxol resistance in ovarian cancer multicellular spheroids.
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.
authors.affiliation: Cancer Biology Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Hubei 430030, P.R. China.
authors.forename: Hui
authors.initials: H
authors.lastname: Xing
authors.forename: Shixuan
authors.initials: S
authors.lastname: Wang
authors.forename: Danhui
authors.initials: D
authors.lastname: Weng
authors.forename: Gang
authors.initials: G
authors.lastname: Chen
authors.forename: Xiaokui
authors.initials: X
authors.lastname: Yang
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Zhou
authors.forename: Gang
authors.initials: G
authors.lastname: Xu
authors.forename: Yunpin
authors.initials: Y
authors.lastname: Lu
authors.forename: Ding
authors.initials: D
authors.lastname: Ma
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D000972:Antineoplastic Agents, Phytogenic / Q000493:pharmacokinetics / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D016376:Oligonucleotides, Antisense / Q000235:genetics; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D017239:Paclitaxel / Q000493:pharmacokinetics / Q000494:pharmacology*; D034741:RNA, Small Interfering / Q000235:genetics; D018874:Spheroids, Cellular; D014162:Transfection
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000972:Antineoplastic Agents, Phytogenic; D016376:Oligonucleotides, Antisense; D034741:RNA, Small Interfering; D050760:Cyclin-Dependent Kinase Inhibitor p27; D017239:Paclitaxel