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Cellular Oncology
Published in: Cellular Oncology 3/2017

01-06-2017 | Original Paper

Inhibition of CDK4 sensitizes multidrug resistant ovarian cancer cells to paclitaxel by increasing apoptosiss

Authors: Yan Gao, Jacson Shen, Edwin Choy, Henry Mankin, Francis Hornicek, Zhenfeng Duan

Published in: Cellular Oncology | Issue 3/2017

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Abstract

Purpose

Overexpression of cyclin-dependent kinase (CDK) 4 has been observed in a variety of cancers and has been found to contribute to tumor cell growth and proliferation. However, the effect of inhibition of CDK4 in ovarian cancer is unknown. We investigated the therapeutic effect of the CDK4 inhibitor palbociclib in combination with paclitaxel in ovarian cancer cells.

Methods

Cell viabilities were determined by MTT assay after exposure to different dosages of palbociclib and/or paclitaxel. Western blot, immunofluorescence, and Calcein AM assays were conducted to determine the mechanisms underlying the cytotoxic effects of palbociclib in combination with paclitaxel. CDK4 siRNA was used to validate the outcome of targeting CDK4 by palbociclib in ovarian cancer cells.

Results

We found that combinations of palbociclib and paclitaxel significantly enhanced drug sensitivity in both Rb-positive (SKOV3TR) and Rb-negative (OVCAR8TR) ovarian cancer-derived cells. When combined with paclitaxel, palbociclib induced apoptosis in both SKOV3TR and OVCAR8TR cells. We also found that palbociclib inhibited the activity of P-glycoprotein (Pgp), and that siRNA-mediated CDK4 knockdown sensitized multidrug resistant (MDR) SKOV3TR and OVCAR8TR cells to paclitaxel.

Conclusions

Inhibition of CDK4 by palbociclib can enhance paclitaxel sensitivity in both Rb-positive and Rb-negative MDR ovarian cancer cells by increasing apoptosis. CDK4 may serve as a promising target in the treatment of ovarian cancer.
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Metadata
Title
Inhibition of CDK4 sensitizes multidrug resistant ovarian cancer cells to paclitaxel by increasing apoptosiss
Authors
Yan Gao
Jacson Shen
Edwin Choy
Henry Mankin
Francis Hornicek
Zhenfeng Duan
Publication date
01-06-2017
Publisher
Springer Netherlands
Published in
Cellular Oncology / Issue 3/2017
Print ISSN: 2211-3428
Electronic ISSN: 2211-3436
DOI
https://doi.org/10.1007/s13402-017-0316-x

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