Effects of different chemotherapeutic agents on reversing the acquired resistance to TRAIL gene in DLD1 colon cancer cells
- VernacularTitle:不同化疗药物对结肠癌细胞获得性TRAIL基因耐药的逆转作用
- Author:
Hongbo ZHU
;
Wenying ZHUO
;
Chao HE
;
Xuefeng HUANG
;
Yuping ZHU
;
Da WANG
;
Bingliang FANG
- Publication Type:Journal Article
- Keywords:
Genes,TRAIL;
Colonic neoplasms;
Drug therapy
- From:
Chinese Journal of Pathophysiology
1986;0(02):-
- CountryChina
- Language:Chinese
-
Abstract:
AIM:To evaluate effects of different chemotherapeutic agents on reversing the acquired resistance to TRAIL gene and clarify the involved mechanisms in DLD1-TRAIL/R colon cancer cells.METHODS: Human colon cancer cell line DLD1-TRAIL/R cells that were resistant to TRAIL-expressing adenovector(Ad/gTRAIL) were treated with Ad/gTRAIL combined with different chemotherapeutic agents.Then,the cell viability was measured by MTT method,and apoptotic signaling conditions,including activation of caspase-3 and caspase-8,expression of Bax and Bcl-XL,were measured by Western blotting analysis.RESULTS: In vitro data showed that several chemotherapeutic agents,including 5-fluorouracil(5-FU) and mitomycin c(MMC),overcome the acquired resistance to TRAIL gene in DLD1-TRAIL/R colon cancer cells.The combination of Ad/gTRAIL and 5-FU effectively suppressed tumor growth in vivo in subcutaneous tumors established from DLD1-TRAIL/R cells.Further data showed that treatment with the combination of Ad/gTRAIL and 5-FU or MMC led to enhance the activation of caspase-3.Moreover,MMC but not 5-FU induced overexpression of Bax gene that was sufficient to overcome the resistance to TRAIL gene in DLD1-TRAIL/R cells.CONCLUSION: Chemotherapeutic agents,such as 5-FU and MMC,overcome the acquired resistance to TRAIL gene in DLD1-TRAIL/R cells.The candidate mechanisms for MMC but not 5-FU to overcome this resistance might involve the induction of over-expressed Bax protein in DLD1-TRAIL/R cells.
