Protein kinase D2 silencing reduced motility of doxorubicin-resistant MCF7 cells
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Success of chemotherapy is generally impaired by multidrug resistance, intrinsic resistance, or acquired resistance to functionally and structurally irrelevant drugs. Multidrug resistance emerges via distinct mechanisms: increased drug export, decreased drug internalization, dysfunctional apoptotic machinery, increased DNA damage repair, altered cell cycle regulation, and increased drug detoxification. Several reports demonstrated that multidrug resistance is a multifaceted problem such that multidrug resistance correlates with increased aggressiveness and metastatic potential. Here, we tested the involvement of protein kinase D2, a serine/threonine kinase that was previously implicated in proliferation, drug resistance, and motility in doxorubicin-resistant MCF7 (MCF7/DOX) cell line, which served as an in vitro model for drug resistance and invasiveness. We showed that basal level activity of protein kinase D2 (PKD2) was higher in MCF7/DOX cells than parental MCF7 cells. To elucidate the roles of PKD2 MCF7/DOX, PKD2 expression was reduced via small interfering RNA (siRNA)-mediated knockdown. Results showed that acquired resistance of MCF7/DOX to doxorubicin was not affected by PKD2 silencing, while motility of MCF7/DOX cells was reduced. The results implied that PKD2 silencing might inhibit migration of MCF7/DOX cells without affecting chemoresistance significantly.
KeywordsMultidrug resistance Breast cancer Migration Protein kinase D2
We thank Assoc. Dr. Özlem Darcansoy İşeri and Assoc. Dr. Meltem Demirel Kars for developing MCF7/DOX subline and Çağrı Urfalı Mamatoğlu for critical reading. We greatly acknowledged Soner Yildiz and Assoc. Prof. Dr. Mayda Gürsel for their contributions in flow cytometry. This work was supported by TUBITAK 1002 Short Term R&D Funding Program (Grant ID: 112T714) and METU Research Fund (Grant ID: BAP-07-02-2012-101-22).
Conflicts of interest
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