Role and mechanism of autophagy in the arsenic trioxide-induced death of Burkitt lymphoma Raji cells
10.3969/j.issn.1001-1978.2014.05.029
- VernacularTitle:自噬在As2O3诱导Burkitt淋巴瘤Raji细胞死亡中的作用及机制研究
- Author:
Caili LI
;
Jing CHEN
;
Bei WANG
;
Feifei WANG
;
Baoying TIAN
;
Bei XIE
;
Linlan FAN
;
Hulai WEI
- Publication Type:Journal Article
- Keywords:
autophagy;
arsenic trioxide (As2O3);
Raji cells;
apoptosis;
Bcl-2;
p53
- From:
Chinese Pharmacological Bulletin
2014;(5):719-724
- CountryChina
- Language:Chinese
-
Abstract:
Aim To investigate the role of autophagy and its mechanism in Raji cell death induced by arse-nic trioxide. Methods Transmission electron micros-copy ( SEM) and MDC fluorescence staining were used to observe autophagy. MTT colorimetry was employed to assay the cellular proliferating activity. Cell apopto-sis and cell cycle analysis were performed using FITC-Annexin-V/PI double staining and flow cytometry ( FCM) . The expressions of LC3 and the conversion of LC3-I to LC3-II were measured by western bloting. The expression of bcl-2 mRNA and p53 mRNA were detected by reverse transcription-polymerase chain re-action ( RT-PCR ) . Results Arsenic trioxide could obviously inhibit the proliferation of Raji cells, arrest the cells at G2/M phase and induce apoptosis. Mean-while, arsenic trioxide markedly inhibited the expres-sion of bcl-2 mRNA and enhanced the expression of p53 mRNA in Raji cells. Arsenic trioxide also induced autophagy synchronously which paralleled with the in-duction of apoptosis in Raji cells, and 3-MA, an auto-phagy inhibitor, was able to reverse the arsenic triox-ide-activated autophagic activity, up-regulate bcl-2, down-regulated p53 expression and suppress the lethal effect of arsenic trioxide on Raji cells to reduce their sensitivity to arsenic trioxide. In contrast, the Rapamy-cin, an autophagy inducer, possessed the completely opposite effects on Raji cells compared with 3-MA. Conclusions The apoptosis and autophagic cell death are coexistent in arsenic trioxide-triggered death of Raji lymphoma cells, and Bcl-2 and p53 may play a key regulating role in this process.
