title: Ephrin type‑A receptor 2 regulates sensitivity to paclitaxel in nasopharyngeal carcinoma via the phosphoinositide 3‑kinase/Akt signalling pathway.
abstract: Ephrin type‑A receptor 2 (EphA2) is a receptor tyrosine kinase that is associated with cancer cell metastasis. There has been little investigation into its impact on the regulation of sensitivity to paclitaxel in nasopharyngeal carcinoma (NPC). In the present study, upregulation of EphA2 expression enhanced the survival of NPC 5‑8F cells, compared with control cells exposed to the same concentrations of paclitaxel. Flow cytometry and western blot analysis demonstrated that over‑expression of EphA2 decreased NPC cancer cell sensitivity to paclitaxel by regulating paclitaxel‑mediated cell cycle progression but not apoptosis in vitro. This was accompanied by alterations in the expression of cyclin‑dependent kinase inhibitors, p21 and p27, and of inactive phosphorylated‑retinoblastoma protein. Furthermore, paclitaxel stimulation and EphA2 over‑expression resulted in activation of the phosphoinositide 3‑kinase (PI3K)/Akt signalling pathway in NPC cells. Inhibition of the PI3K/Akt signalling pathway restored sensitivity to paclitaxel in 5‑8F cells over‑expressing EphA2, which indicated that the PI3K/Akt pathway is involved in EphA2‑mediated paclitaxel sensitivity. The current study demonstrated that EphA2 mediates sensitivity to paclitaxel via the regulation of the PI3K/Akt signalling pathway in NPC.
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Yunyun
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Guo
authors.initials: G
authors.lastname: Li
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Zhongwu
authors.initials: Z
authors.lastname: Su
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Shuling
authors.initials: S
authors.lastname: Ren
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Pingqing
authors.initials: P
authors.lastname: Tan
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Yuanzheng
authors.initials: Y
authors.lastname: Qiu
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Yongquan
authors.initials: Y
authors.lastname: Tian
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002277:Carcinoma; D045744:Cell Line, Tumor / Q000187:drug effects; D019927:Cyclin E / Q000235:genetics / Q000378:metabolism; D051357:Cyclin-Dependent Kinase 2 / Q000235:genetics / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics / Q000378:metabolism; D018844:Cyclin-Dependent Kinases / Q000235:genetics / Q000378:metabolism; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000378:metabolism / Q000473:pathology*; D017239:Paclitaxel / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D011817:Rabbits; D036104:Receptor, EphA2 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D019927:Cyclin E; D050759:Cyclin-Dependent Kinase Inhibitor p21; D050760:Cyclin-Dependent Kinase Inhibitor p27; D019869:Phosphatidylinositol 3-Kinases; D036104:Receptor, EphA2; D051057:Proto-Oncogene Proteins c-akt; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases; D017239:Paclitaxel