title: Nek2-targeted ASO or siRNA pretreatment enhances anticancer drug sensitivity             in triple‑negative breast cancer cells.
abstract: Although the anticancer drugs paclitaxel and doxorubicin are commonly used             to treat many solid tumors, their effectiveness is highly variable due to tumor             cell resistance. Therefore, it is important to find mechanisms that can be targeted             to increase the sensitivity of cancer cells to current chemotherapeutic agents.             NIMA‑related kinase 2 (Nek2), a serine/threonine kinase is emerging as an important             oncogene because of its regulatory role in mitosis. Thus, regulation of the Nek2             expression levels may prove important as a target for cancer treatment. The purpose             of our study was to determine whether drug sensitivity was increased in the triple             negative breast cancer cell lines MDA-MB-231 and MDA-MB-468 by using small interfering             RNA (siRNA) and antisense oligonucleotides (ASOs) against Nek2. To this end, MDA-MB-231             and MDA-MB-468 breast cancer cells transfected with Nek2 siRNA or ASO were exposed             to various concentrations of paclitaxel and doxorubicin. Cell viability, cell             cycle distribution and apoptosis were evaluated. We observed that drug susceptibility             in these transfected cells was dramatically increased compared with either agent             alone. FACS results showed that apoptosis was induced in siRNA- and ASO‑transfected             cells as expected due to the regulatory function of Nek2 in centrosome duplication.             Interestingly, the cell cyle was not arrested in transfected cells. We found that             siRNA and ASO against Nek2 worked synergistically with paclitaxel and doxorubicin             by promoting cell apoptosis. Our results suggest that these drugs in combination             with Nek2 siRNA or ASO treatment may improve the sensitivity of cancer cells during             chemotherapy treatments.
authors: Department of Biological Sciences, Texas Tech University, Lubbock, TX 79409-3131, USA.
authors: Jaehyung
authors: J
authors: Lee
authors: Lauren
authors: L
authors: Gollahon
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D001943:Breast Neoplasms / Q000188:drug therapy*; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D004317:Doxorubicin / Q000494:pharmacology / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D006801:Humans; D000072379:NIMA-Related Kinases; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000494:pharmacology*; D017239:Paclitaxel / Q000494:pharmacology / Q000627:therapeutic use; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics / Q000494:pharmacology*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D008941:Spindle Apparatus
chemical_list: D000970:Antineoplastic Agents; D004317:Doxorubicin; D000072379:NIMA-Related Kinases; D016376:Oligonucleotides, Antisense; D017239:Paclitaxel; D017346:Protein Serine-Threonine Kinases; D034741:RNA, Small Interfering; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C089441:NEK2 protein, human