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Ephrin type‑A receptor 2 regulates sensitivity to paclitaxel in nasopharyngeal carcinoma via the phosphoinositide 3‑kinase/Akt signalling pathway.

Wang Y, Liu Y, Li G, Su Z, Ren S, Tan P, Zhang X, Qiu Y, Tian Y - Mol Med Rep (2014)

Bottom Line: 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.Furthermore, paclitaxel stimulation and EphA2 over‑expression resulted in activation of the phosphoinositide 3‑kinase (PI3K)/Akt signalling pathway in NPC cells.The current study demonstrated that EphA2 mediates sensitivity to paclitaxel via the regulation of the PI3K/Akt signalling pathway in NPC.

View Article: PubMed Central - PubMed

Affiliation: Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.

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.

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Effect of EphA2 over-expression on cyclin-dependent kinase inhibitors, p21Cip1 and p27Kip1, in NPC 5-8F cells. Western blot analysis was used to detect the expression of p21Cip1, p27Kip1 CDK2, Cyclin E and p-Rb in NPC 5-8F and CNE-2 nasopharyngeal carcinoma cells. All data were obtained by three independent experiments, which produced similar results. EphA2, ephrin type-A receptor 2; CDK, cyclin-dependent kinase; Rb, retinoblastoma protein; p-Rb, phosphorylated Rb; NPC, nasopharyngeal carcinoma.
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f3-mmr-11-02-0924: Effect of EphA2 over-expression on cyclin-dependent kinase inhibitors, p21Cip1 and p27Kip1, in NPC 5-8F cells. Western blot analysis was used to detect the expression of p21Cip1, p27Kip1 CDK2, Cyclin E and p-Rb in NPC 5-8F and CNE-2 nasopharyngeal carcinoma cells. All data were obtained by three independent experiments, which produced similar results. EphA2, ephrin type-A receptor 2; CDK, cyclin-dependent kinase; Rb, retinoblastoma protein; p-Rb, phosphorylated Rb; NPC, nasopharyngeal carcinoma.

Mentions: Since EphA2 expression was associated with changes in cell cycle progression following administration of paclitaxel, the regulation of cell cycle factors by EphA2 was investigated. Western blot analyses indicated that ectopic expression of EphA2 did not influence the expression of the cell cycle promoters, CDK2 and Cyclin E, whereas the expression of cyclin-dependent kinase inhibitors, p21 and p27, were significantly downregulated. In addition, the expression of inactive p-Rb was increased without a change in the total expression of Rb, which is also an inhibitory factor in cell cycle progression (Fig. 3).


Ephrin type‑A receptor 2 regulates sensitivity to paclitaxel in nasopharyngeal carcinoma via the phosphoinositide 3‑kinase/Akt signalling pathway.

Wang Y, Liu Y, Li G, Su Z, Ren S, Tan P, Zhang X, Qiu Y, Tian Y - Mol Med Rep (2014)

Effect of EphA2 over-expression on cyclin-dependent kinase inhibitors, p21Cip1 and p27Kip1, in NPC 5-8F cells. Western blot analysis was used to detect the expression of p21Cip1, p27Kip1 CDK2, Cyclin E and p-Rb in NPC 5-8F and CNE-2 nasopharyngeal carcinoma cells. All data were obtained by three independent experiments, which produced similar results. EphA2, ephrin type-A receptor 2; CDK, cyclin-dependent kinase; Rb, retinoblastoma protein; p-Rb, phosphorylated Rb; NPC, nasopharyngeal carcinoma.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4262504&req=5

f3-mmr-11-02-0924: Effect of EphA2 over-expression on cyclin-dependent kinase inhibitors, p21Cip1 and p27Kip1, in NPC 5-8F cells. Western blot analysis was used to detect the expression of p21Cip1, p27Kip1 CDK2, Cyclin E and p-Rb in NPC 5-8F and CNE-2 nasopharyngeal carcinoma cells. All data were obtained by three independent experiments, which produced similar results. EphA2, ephrin type-A receptor 2; CDK, cyclin-dependent kinase; Rb, retinoblastoma protein; p-Rb, phosphorylated Rb; NPC, nasopharyngeal carcinoma.
Mentions: Since EphA2 expression was associated with changes in cell cycle progression following administration of paclitaxel, the regulation of cell cycle factors by EphA2 was investigated. Western blot analyses indicated that ectopic expression of EphA2 did not influence the expression of the cell cycle promoters, CDK2 and Cyclin E, whereas the expression of cyclin-dependent kinase inhibitors, p21 and p27, were significantly downregulated. In addition, the expression of inactive p-Rb was increased without a change in the total expression of Rb, which is also an inhibitory factor in cell cycle progression (Fig. 3).

Bottom Line: 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.Furthermore, paclitaxel stimulation and EphA2 over‑expression resulted in activation of the phosphoinositide 3‑kinase (PI3K)/Akt signalling pathway in NPC cells.The current study demonstrated that EphA2 mediates sensitivity to paclitaxel via the regulation of the PI3K/Akt signalling pathway in NPC.

View Article: PubMed Central - PubMed

Affiliation: Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.

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.

Show MeSH
Related in: MedlinePlus