Effects of azidothymidine on p33ING1b expression, apoptosis and senescence of TJ905 human glioblastoma cell line.
- Author:
Qian WANG
1
;
Shi-zhu YU
;
Wen-juan ZHAO
;
Jing LIU
;
Cui-yun SUN
;
Tong-ling AN
;
Li-li WANG
;
Xiao-li REN
;
Xiu-ju CHEN
Author Information
- Publication Type:Journal Article
- MeSH: Apoptosis; drug effects; Brain Neoplasms; metabolism; pathology; Cell Line, Tumor; Cellular Senescence; drug effects; Dose-Response Relationship, Drug; Glioblastoma; metabolism; pathology; Humans; Inhibitor of Growth Protein 1; Intracellular Signaling Peptides and Proteins; genetics; metabolism; Nuclear Proteins; genetics; metabolism; RNA, Messenger; metabolism; Reverse Transcriptase Inhibitors; administration & dosage; pharmacology; Reverse Transcriptase Polymerase Chain Reaction; Tumor Suppressor Proteins; genetics; metabolism; Zidovudine; administration & dosage; pharmacology
- From: Chinese Journal of Pathology 2010;39(10):686-690
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVESTo investigate the pharmacological effects of azidothymidine (AZT) on p33ING1b expression, senescence and apoptosis of TJ905 glioblastoma cells.
METHODSTJ905 cells were treated with AZT at a serial concentrations of 50, 100 and 200 µmol/L. Semi-quantitative RT-PCR and cytochemical staining of senescence related-galactosidase (sβ-Gal) were used to evaluate the expression of p33ING1b mRNA and to label the senescent cells at the 1st, 3rd and 6th generations, respectively. In situ cell death detection and single cell gel electrophoresis were used to detect the apoptosis at the 3rd and 6th generations.
RESULTSAZT induced the expression of p33ING1b mRNA and senescence of the tumor cells of the 1st generation in a dosage and time dependent manner. At the 6th generation, the relative amount of p33ING1b RT-PCR product (1.44±0.23) and sβ-Gal labeling index of 200 µmol/L group (45.62±6.74) were significantly higher than those of the 1st (0.95±0.13 and 7.82±2.40) and the 3rd generation cells (1.35±0.23, 26.27±7.17) of the same group, and cells of the same generation in the 50 µmol/L (0.85±0.24, 27.37±6.41) and 100 µmol/L groups (1.23±0.34, 35.49±5.12, P<0.01). There was a significant positive correlation between the p33ING1b mRNA expression and the labeling index of sβ-Gal. Pro-apoptotic effects of AZT became obvious at the 6th generation.
CONCLUSIONAZT upregulates the expression of p33ING1b, a possible mechanism in regulating senescence and apoptosis of the TJ905 cells.