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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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Effects of EphA2 on paclitaxel sensitivity of nasopharyngeal carcinoma 5-8F cells in vitro. (A) Western blot analysis was conducted to confirm the efficiency of EphA2 over-expression. (B) Proliferation assay curves of each group. EphA2, ephrin type-A receptor 2.
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f1-mmr-11-02-0924: Effects of EphA2 on paclitaxel sensitivity of nasopharyngeal carcinoma 5-8F cells in vitro. (A) Western blot analysis was conducted to confirm the efficiency of EphA2 over-expression. (B) Proliferation assay curves of each group. EphA2, ephrin type-A receptor 2.

Mentions: A preliminary study demonstrated that EphA2 silencing led to increased sensitivity of 5-8F NPC cells to paclitaxel in vitro (23). To confirm the association between EphA2 and NPC sensitivity to paclitaxel, an EphA2 cDNA-pEGFP-N1 expression plasmid was used to upregulate EphA2 expression in 5-8F NPC cells. As shown in Fig. 1A, EphA2 was demonstrated to be successfully upregulated in EphA2 cDNA plasmid-transfected 5-8F cells compared with parent and vector plasmid-transfected 5-8F cells. Following paclitaxel stimulation with varying concentrations for 48 h, paclitaxel IC50 values in EphA2 cDNA plasmid-transfected, parent and vector plasmid-transfected 5-8F cells were 3.8±0.52, 1.3±0.06 and 1.4±0.05 nM/l, respectively, indicating that EphA2 upregulation enhanced the survival of 5-8F NPC cells compared with control cells exposed to the same concentrations of paclitaxel (Fig. 1B). These results confirmed the involvement of EphA2 in the sensitivity of NPC cells to paclitaxel.


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)

Effects of EphA2 on paclitaxel sensitivity of nasopharyngeal carcinoma 5-8F cells in vitro. (A) Western blot analysis was conducted to confirm the efficiency of EphA2 over-expression. (B) Proliferation assay curves of each group. EphA2, ephrin type-A receptor 2.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f1-mmr-11-02-0924: Effects of EphA2 on paclitaxel sensitivity of nasopharyngeal carcinoma 5-8F cells in vitro. (A) Western blot analysis was conducted to confirm the efficiency of EphA2 over-expression. (B) Proliferation assay curves of each group. EphA2, ephrin type-A receptor 2.
Mentions: A preliminary study demonstrated that EphA2 silencing led to increased sensitivity of 5-8F NPC cells to paclitaxel in vitro (23). To confirm the association between EphA2 and NPC sensitivity to paclitaxel, an EphA2 cDNA-pEGFP-N1 expression plasmid was used to upregulate EphA2 expression in 5-8F NPC cells. As shown in Fig. 1A, EphA2 was demonstrated to be successfully upregulated in EphA2 cDNA plasmid-transfected 5-8F cells compared with parent and vector plasmid-transfected 5-8F cells. Following paclitaxel stimulation with varying concentrations for 48 h, paclitaxel IC50 values in EphA2 cDNA plasmid-transfected, parent and vector plasmid-transfected 5-8F cells were 3.8±0.52, 1.3±0.06 and 1.4±0.05 nM/l, respectively, indicating that EphA2 upregulation enhanced the survival of 5-8F NPC cells compared with control cells exposed to the same concentrations of paclitaxel (Fig. 1B). These results confirmed the involvement of EphA2 in the sensitivity of NPC cells to paclitaxel.

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