Study of signal transduction mechanisms of X-ray induced multidrug resistance in nasopharyngeal squamous cell carcinoma CNE1 cells / 国际肿瘤学杂志

ABSTRACT

Objective To investigate the relationship between multidrug resistance of X-ray irradiated human nasopharyngeal squanous carcinoma cell line CNE1 and platelet endothelial cell adhesion molecule-1 (PECMA-1)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/Bcl-2 signaling pathway.Methods ①The CNE1 cells were cultured in incubator.Exponentially growing CNE1 cells were exposed to 50 Gy ionizing radiation administered in 25 fractions,2 Gy per fraction,once every two days,and the CNE1/R cells were collected.②CNE1/R cells were cultured for 24 h,and divided into three groupsthe control group,experimental group one (CNE1/R cells were processed through 1 ∶ 600 PECAM-1 antibody for 24 h) and experimental group two (CNE1/R cells were processed through 10 μmol/L PI3K inhibitor LY294002 for 24 h).③The half maximal inhibitory concentration (IC50) values of the control group and two experimental groups of CNE1/R cells were detected by methyl thiazolyl tetrazolium (MTT).④The mRNA expressions of PI3K and Bcl-2 in the control group and experimental group one were measured by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR).⑤The mRNA expressions of AKT and Bcl-2 in the control group and experimental group two were measured by semi-quantitative RT-PCR.Results ①The IC50 of the control group,experimental group one and two were (2.99 ± 0.02) μg/ml,(1.50 ± 0.03) μg/ml and (1.60 ±0.05)μg/ml,and the difference among the three groups was statiatically signficant (F =4 381.263,P =0.000).The IC50 of the two experimental groups were obviously lower than that of the control group (t =116.885,P =0.000;t =73.006,P =0.000).②The semi-quantitative values of PI3K in the control group and experimental group one were 1.66 ±0.01 and 0.90 ±0.05 (t =50.394,P =0.000),and the semi-quantitative values of Bcl-2 were 1.66 ±0.02 and 0.71 0.05 (t =183.165,P =0.000),and the differences were statistically significant.③The semi-quantitative values of AKT of control group and experimental group two were 1.53 ± 0.01 and 0.72 ± 0.01 (t =135.281,P =0.000),and the semi-quantitative values of Bel-2 were 1.66 ± 0.02 and 0.63 ± 0.02 (t =128.814,P =0.000),and the differences were statistically significant.Conclusion PECAM-1 induced multidmg resistance of human nasopharyngeal squamous cell carcinoma CNE1 cells may be related to the activity of Bcl-2 through the signal pathway of PI3K/AKT.