An Experimental Study Of Establishment Of Multidrug Resistance Cell Line LOVO/5-FU Of Human Colorectal Cancer And Its Biological Characters

PURPOSE: To establish multidrug resistant cell line LQVOI5-FU of human colorectal cancer and investigate it's MDR mechanism. METHODS: A multidrug resistant variant of human colorectal cancer resistant to 5-FU ,LOVO/5-FU has been establish in vitro by exposing LOVO parent cell to pulse treatment with 2.5ug/ml of the drug over a period of 6 month .Its IC50 to variant antitumor agents was detected by MTT method .The morphology was observed by light microscope and electron microscope . The apoptosis caused by 5-FU was detected by morphology change under light microcope .DAN strand breaks techniques and in situ tabeling Bcl-2 gene expression on LOVO andLOVO/5-FU was detected by immunohistochemical staining. BESULTS : The LOVQ/5-FU cell was times more resistant to 5-FU than the LOVO parent cells. LOVO/5-FU exhibited cross-resistant to 5-FU~ MMC. ADM . DDP, but not to CTX., Arac .Compared to the parent cells ,the resistant cells have a slowed growth rate and lower confluent density ,unlike the LOVO parent cells . The expression of Bcl-2 gene on LQVO and LOVO/5-FU cells was positive and the positive staining was in the cyto- plasm . Compared to the parent cell the resistant cells have a higher in the Bcl-2express. CONCLUSIONS: 1 : The changes of biological characters of LQVO/5-FU probably related with the MDR phenotype .2 Both of LOVO and LOVO/5- FU cells underwent apoptosis after exposure to 5-FU.The importment mechanism of 5-FU killing carcinoma cell is due to cells抋poptosis .3 : MDR is an importment phenomenon in colorectal cancer and that more than one pathway of MDR may be present in human colorectal cancer cell lines .4 LOVO/5-FU may be a useful model for the development of new chemotherapeutic strategies in overcoming drug-resistance in the treatment of colorectal cancer .5:The LOVO/5-FU cells can resist the apoptosis which was caused by 5-FU .Itsmechanism might be closely related with the overexpression of p26-bcl-2 . 6: The overexpression of bcl-2 may be the important mechanism for colorectal cancer MDR.