[The lethal effect of combined MDR1 antisense RNA with oxaliplatin and 5-FU on drug-resistant rectal carcinoma cells].
OBJECTIVE
To observe the lethal effect of multidrug resistance gene (MDR1) antisense RNA combined with oxaliplatin and 5-FU on drug-resistant rectal carcinoma cells.


METHODS
PC-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.


RESULTS
A 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.


CONCLUSIONS
Combined 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.
Chen
Gang
G
Department of General Surgery, General Hospital of Beijing Command, People's Liberation Army, Beijing 100700, China. fayzhao@163.com
Li
Shi-yong
SY
Yu
Bo
B
An
Ping
P
Cai
Hui-yun
HY
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D004357:Drug Synergism; D005472:Fluorouracil / Q000494:pharmacology*; D019450:Genes, MDR / Q000235:genetics*; D015316:Genetic Therapy; D006801:Humans; D009944:Organoplatinum Compounds / Q000494:pharmacology*; D000077150:Oxaliplatin; D016372:RNA, Antisense / Q000235:genetics*; D012004:Rectal Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D014162:Transfection
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D016372:RNA, Antisense; D000077150:Oxaliplatin; D005472:Fluorouracil