Study on effect of recombinant adenovirus PUMA on sensitivity of human glioblastoma cells to temozolomide in vivo
10.3760/cma.j.issn.1006-9801.2011.03.002
- VernacularTitle:重组腺病毒P53上调凋亡调控因子增强胶质瘤细胞对替莫唑胺敏感性的体内研究
- Author:
Xiaodong LIU
;
Hongqin WANG
;
Wang MIAO
;
Heqian ZHAO
;
Yimin FAN
;
Jiehe HAO
- Publication Type:Journal Article
- Keywords:
Glioma;
Temozolomide;
p53 up-regulated modulator of apoptosis;
Recombinant adenovirus
- From:
Cancer Research and Clinic
2011;23(3):150-153
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the inhibitive effects of Ad-PUMA combined with temozolomide on human glioblastoma cells growth in vivo experiments. Methods The nude mouse model with human glioblastoma cells subcutaneous transplantation was established. The mice were randomly divided into 4 groups to receive subcutaneous injection at the 14th day separately with: Normal saline 100 μl (control, n=8), Ad-PUMA 2×108 pfu/100 μl (PUMA group, n=8), 10 mg/kg TMZ (TMZ group, n=8) and 2×108 pfu/100 μl Ad-PUMA + 10 mg/kg TMZ (combined group, n=8). Mice were killed after 20 days treatment.Tumor volume, inhibition rates and apoptotic index (AI) were measured, meanwhile, apoptotic tumor cells were detected by TUNEL technology respectively. The expression of MGMT mRNA and MGMT protein were revealed by the methods of RT-PCR and Western blot. Results According to the order: control group, AdPUMA group, TMZ group, combined group, tumor volumes were (3.68±0.09), (2.63±0.13), (2.13±0.07),(0.97±0.02) cm3 respectively (P＜0.05); the inhibitive rates were 0, 28.5 %, 42.1%, 73.6 % respectively and AI were (2.0±1.2) %, (11.4±2.6) %, (7.6±3.2) %, (20.6±8.6) % (P＜0.05). The results of Western blot and RT-PCR showed that MGMT mRNA and MGMT protein levels in TMZ group were higher than other groups (all P＜0.01). Conclusion Ad-PUMA combined with TMZ greatly enhances the sensitivity of human glioblastoma cells to TMZ and could effectively inhibit the proliferation and promote the apeptosis of glioblastoma cells, its mechanism was probably related Ad-PUMA promote apoptosis and inhibit MGMT expression.
