The lethal effect of combined MDR1 antisense RNA with oxaliplatin and 5-FU on drug-resistant rectal carcinoma cells.
- Author:
Gang CHEN
1
;
Shi-yong LI
;
Bo YU
;
Ping AN
;
Hui-yun CAI
Author Information
- Publication Type:Journal Article
- MeSH: Antineoplastic Agents; pharmacology; Apoptosis; drug effects; Cell Cycle; drug effects; Cell Line, Tumor; Combined Modality Therapy; Drug Synergism; Fluorouracil; pharmacology; Genes, MDR; genetics; Genetic Therapy; Humans; Organoplatinum Compounds; pharmacology; RNA, Antisense; genetics; Rectal Neoplasms; genetics; pathology; therapy; Transfection
- From: Chinese Journal of Surgery 2006;44(11):770-773
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo observe the lethal effect of multidrug resistance gene (MDR1) antisense RNA combined with oxaliplatin and 5-FU on drug-resistant rectal carcinoma cells.
METHODSPC-MDR1 plasmid including MDR1 was constructed with gene cloning techniques. The drug-resistant cancer cells (8348R) were transferred with the plasmids, and the positive neoplasm cells were selected with G418. Green fluorescent protein (GFP) gene was used as a reporting gene to monitor the gene transfer efficiency under the influence of oxaliplatin and 5-FU. The cytotoxicity and therapeutic effects of MDR1 anti-sense RNA combined with oxaliplatin and 5-FU were evaluated by colony-forming rate and MTT assay.
RESULTSA significant decrease of biological activity was observed in 8348R cells transferred with PC-MDR1, cell cycles were blocked in S phase, or in G2/M phase, and apoptosis rate of the cells increased. With treatment of oxaliplatin, the plasmid transfer efficiency in the drug-resistant cancer cells was improved about 18 times. Using an IC(50) dose of oxaliplatin and 5-FU combined with (MDR1) anti-sense RNA, 75 percent of 8348R cells were killed, which was significant higher than that of the control cells.
CONCLUSIONSCombined MDR1 antisense RNA with oxaliplatin and 5-FU has a synergistic effect of killing drug-resistant cancer cells and may be a promising method for treating drug-resistant rectal carcinoma.