Mechanism of apoptosis of HCC HepG2 cells induced with replication-defective virus carrying mda-7 in combination with ardriamycin
10.3760/cma.j.issn.1007-8118.2010.10.019
- VernacularTitle:携带mda-7基因的复制缺陷性腺病毒联合阿霉素致肝癌细胞HepG2凋亡机制的研究
- Author:
Jianwei ZHENG
;
Xinbo XUE
;
Congjun WANG
;
Xiaomei ZHANG
;
Kun CHEN
;
Yan LI
;
Yuan YU
;
Chaowen XIAO
;
Zhihai PENG
;
Jilin YI
;
Zaide WU
- Publication Type:Journal Article
- Keywords:
Hepatocellular carcinoma;
Adriamycin;
Multidrug resistance;
Apoptosis
- From:
Chinese Journal of Hepatobiliary Surgery
2010;16(10):770-776
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the mechanism of melanoma differentiation associated gene-7(mda-7) in combination with adriamycin(ADM) killing the HCC HepG2 cells and reversing their multidrug resistance (MDR). Methods The experiment was conducted in three groups including the combined group, ADM group and mda-7 group. MTT assay and FCM were used to determine the differences among the 3 groups and clarify the reversing effect of combined treatment on multidrug resistance of the tumor cells. Expression levels of MDR-1, STAT-3, BCL-2, BAXmRNA were determined with real-time PCR. Western blotting was performed to observe the changes of proteins gp-l70, stat3,P-stat3, PKB, bcl-2,bax in all 3 groups. Result After transfection with 100VP/cell Ad. mda-7,the growth suppression rate of HepG2 treated by ADM (1.5 mg/L) rose from 17.46% to 79. 5%.According to the changes, killed HepG2 cells were increased by a factor of 4.55. times. MDR-1 mRNA was decreased from (16.49 ± 0. 11) to (5.48±0.05) and STAT-3 mRNA increased from (13.17±0. 08) to (21. 57±0. 11)(P＜0.05). Western blotting also showed that P-170 and PKB was decreased and the phosphorylation-stat-3 increased after the combined treatment. Conclusion Ad.mda-7 can reverse the multidrug resistance HepG2 cells. It inhibits the expression of MDR-1 mRNA,then arrests PKB protein and the signaling pathway of active stat-3 to induce apoptosis of HCC cells.
