Increased sensitivity of colorectal cancer cell lines with microsatellite instability to 5-fluorouracil in vitro.
OBJECTIVE
To study the relationship between sensitivity to 5-FU and the status of a panel of microsatellite loci in three human colon cancer cell lines.


METHODS
Cell viability in several concentrations of 5-FU was assessed by the MTT test. Expression of hMSH2 and hMLH1 in LoVo, SW480 and SW1116 cells were analyzed by immunocytochemical staining.Ten mononucleotide and dinucleotide microsatellite loci were analyzed by the PCR-SSLP-silver staining method.


RESULTS
By MTT assay, it showed that LoVo cells were more sensitive than SW480 and SW1116 cells (0.8 micromol/L,2.2 micromol/L and 1.9 micromol/L, respectively, P < 0.05). By immunocytochemical staining, hMSH2 was expressed in SW480 and SW1116 cells but not in LoVo cells, while hMLH1 was positive in all three cell lines. The PCR-SSLP-silver staining of 10 microsatellite loci revealed that LoVo cells had a different pattern of electrophoretic bands compared with SW480 and SW1116 cells, manifesting both additions and band-shifts.


CONCLUSIONS
Together with hMSH2 and hMLH1, the status of a panel of microsatellite loci may be used as convenient predictors for drug-optimization or prognosis-assessment in colorectal cancer patients before chemotherapy.
Chen
Xiuxu
X
Department of Pathology, School of Medicine, Zhejiang University, Hangzhou 310031, China.
Lai
Mao-de
MD
Huang
Qiong
Q
D048868:Adaptor Proteins, Signal Transducing; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D020137:Base Pair Mismatch; D002352:Carrier Proteins; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D004260:DNA Repair; D004268:DNA-Binding Proteins; D005472:Fluorouracil / Q000494:pharmacology*; D006801:Humans; D007150:Immunohistochemistry; D018895:Microsatellite Repeats; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D009363:Neoplasm Proteins / Q000235:genetics; D009687:Nuclear Proteins; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins / Q000235:genetics; D014407:Tumor Cells, Cultured
D048868:Adaptor Proteins, Signal Transducing; D000964:Antimetabolites, Antineoplastic; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C501486:MLH1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D005472:Fluorouracil