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Title of Journal: J Cancer Res Clin Oncol

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Abbravation: Journal of Cancer Research and Clinical Oncology

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Springer-Verlag

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DOI

10.1007/s13157-016-0767-2

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1432-1335

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Effect of the cyclindependent kinases inhibitor p

Authors: Hui Xing Shixuan Wang Keqin Hu Wenming Tao Jing Li Qinglai Gao Xiaokui Yang Danhui Weng Yunpin Lu Ding Ma
Publish Date: 2005/05/28
Volume: 131, Issue: 8, Pages: 511-519
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Abstract

Purpose A low proliferating fraction in solid tumors limits the effectiveness of cellcycledependent chemotherapeutic agents To understand the molecular basis of such resistance we examined the expression of the cyclindependent kinases inhibitor p27 and relationship with drug resistance and Pgp expression in ovarian cancer multicellular spheroids Methods We cultured ovarian cancer cells A2780 and CAOV3 as multicellular spheroids and examined the expression of p27 and Pglycoprotein Pgp by western blot flow cytometry and confocal We also analyzed the cellcycle distribution by flow cytometry In addition trypan blue exclusion testing and cell apoptosis analysis were used to detect the sensitivity to Taxol Results When transferred from monolayer to threedimensional culture a consistent upregulation of p27 protein and Pgp protein was observed in ovarian cancer cell lines Compared with monolayer cells there was a significant increase of G0G1 phase cells and decrease of S and G2M phase cells in spheroid cells Aggregates of cells showed higher cell viability than monolayer cells Antisense oligodeoxynucleotide ASON mediated downregulation of p27 reduced intercellular adhesion increased cell proliferation downregulated Pgp expression and sensitized cells to Taxol Conclusions Our results implicate that p27 serves as a regulator of drug resistance in ovarian tumors ASONmediated alteration of p27 reverses resistance of ovarian cancer to anticancer agents that are associated with increased sensitivity of ovarian cancer cells to chemotherapeutic agents

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