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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 cell-cycle distribution and apoptosis following exposure to paclitaxel. (A) Graphs of cell cycle distribution in each group. (B) Percentages of cells in different cell cycle phases in each group. (C) Graphs showing apoptosis in each group. (D) Percentage of apoptotic cells in each group. Results are presented as the mean ± standard deviation of at least three independent experiments. *P<0.05. FITC, fluorescein isothiocyanate; EphA2, ephrin type-A receptor 2.
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f2-mmr-11-02-0924: Effect of EphA2 over-expression on cell-cycle distribution and apoptosis following exposure to paclitaxel. (A) Graphs of cell cycle distribution in each group. (B) Percentages of cells in different cell cycle phases in each group. (C) Graphs showing apoptosis in each group. (D) Percentage of apoptotic cells in each group. Results are presented as the mean ± standard deviation of at least three independent experiments. *P<0.05. FITC, fluorescein isothiocyanate; EphA2, ephrin type-A receptor 2.

Mentions: To investigate the mechanisms underlying EphA2-regulated sensitivity of NPC cells to paclitaxel, changes in cell cycle progression and apoptosis in NPC 5-8F cells, following over-expression of EphA2 and the administration of paclitaxel, were assayed by FCM. The percentage of cells in G0/G1 phase in the 5-8F cells transfected with the EphA2 cDNA plasmid was significantly reduced compared with that in the parent and vector plasmid transfected 5-8F cells (45.76±3.89 compared with 64.52±3.31 and 65.85±2.28%, respectively; P<0.05). By contrast, the percentage of cells in the S phase (31.56±1.59 compared with 24.55±3.64 and 25.76±1.89%, respectively; P<0.05) and the G2/M phase (23.10±4.55 compared with 10.94±3.27 and 8.39±0.81%, respectively; P<0.05) were significantly increased in cells over-expressing EphA2 compared with the other groups (Fig. 2A and B). However, the percentage of apoptotic cells in these three groups was not significantly different, with that of the EphA2-over-expressed group (9.84±2.08) similar to those of the parental (8.66±1.5) and vector (7.74±1.34%) groups (P>0.05) (Fig. 2C and D). These results demonstrate that EphA2 over-expression regulated paclitaxel-mediated cell-cycle progression but not apoptosis in NPC cells.


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 cell-cycle distribution and apoptosis following exposure to paclitaxel. (A) Graphs of cell cycle distribution in each group. (B) Percentages of cells in different cell cycle phases in each group. (C) Graphs showing apoptosis in each group. (D) Percentage of apoptotic cells in each group. Results are presented as the mean ± standard deviation of at least three independent experiments. *P<0.05. FITC, fluorescein isothiocyanate; EphA2, ephrin type-A receptor 2.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f2-mmr-11-02-0924: Effect of EphA2 over-expression on cell-cycle distribution and apoptosis following exposure to paclitaxel. (A) Graphs of cell cycle distribution in each group. (B) Percentages of cells in different cell cycle phases in each group. (C) Graphs showing apoptosis in each group. (D) Percentage of apoptotic cells in each group. Results are presented as the mean ± standard deviation of at least three independent experiments. *P<0.05. FITC, fluorescein isothiocyanate; EphA2, ephrin type-A receptor 2.
Mentions: To investigate the mechanisms underlying EphA2-regulated sensitivity of NPC cells to paclitaxel, changes in cell cycle progression and apoptosis in NPC 5-8F cells, following over-expression of EphA2 and the administration of paclitaxel, were assayed by FCM. The percentage of cells in G0/G1 phase in the 5-8F cells transfected with the EphA2 cDNA plasmid was significantly reduced compared with that in the parent and vector plasmid transfected 5-8F cells (45.76±3.89 compared with 64.52±3.31 and 65.85±2.28%, respectively; P<0.05). By contrast, the percentage of cells in the S phase (31.56±1.59 compared with 24.55±3.64 and 25.76±1.89%, respectively; P<0.05) and the G2/M phase (23.10±4.55 compared with 10.94±3.27 and 8.39±0.81%, respectively; P<0.05) were significantly increased in cells over-expressing EphA2 compared with the other groups (Fig. 2A and B). However, the percentage of apoptotic cells in these three groups was not significantly different, with that of the EphA2-over-expressed group (9.84±2.08) similar to those of the parental (8.66±1.5) and vector (7.74±1.34%) groups (P>0.05) (Fig. 2C and D). These results demonstrate that EphA2 over-expression regulated paclitaxel-mediated cell-cycle progression but not apoptosis in NPC cells.

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