Effect of levamisole on major histocompatibility complex class I expression in colorectal and breast carcinoma cell lines.
BACKGROUND
The antihelminthic drug levamisole (LMS) is used in conjunction with 5-fluorouracil (5-FU) as adjuvant therapy to reduce the incidence of colon cancer relapse following surgical resection. Clinical trials in patients with breast cancer have yielded conflicting results as to its efficacy in the treatment of this malignancy. LMS is thought to act as an immunostimulant, yet its precise mechanism remains unclear. In this study, the effect of LMS on major histocompatibility complex (MHC) class I (MHC I) and MHC class II (MHC II) expressions in human colorectal and breast carcinoma cell lines was examined.


METHODS
The colon cancer cell line CaCo-2 and the breast cancer cell line MDA-MB-435 were cultured for 24-68 hours in the presence or absence of 10-microns LMS followed by staining with antibodies directed against either MHC I or MHC II: After staining, cells were visualized by fluorescent microscopy.


RESULTS
When cultured in the presence of LMS, cells from both cell lines exhibited a decreased fluorescent intensity with antibodies directed against MHC I protein. The most significant difference from cells cultured without LMS was apparent after 48 hours of incubation. Neither cell line exhibited fluorescent intensities above background when stained with anti-MHC II antibody.


CONCLUSIONS
LMS decreases the expression of MHC I on CaCo-2 and MDA-MB-435 tumor cell lines. Prior studies have indicated that natural killer (NK) cells are more efficient in attacking cells with lowered or no MHC I expression. An MHC I deficiency induced by LMS would augment NK-mediated immune surveillance. One mechanism contributing to levamisole's anti-tumor activity in vivo may be reduction of MHC I expression on tumor cells.
Goodrich
K H
KH
Department of Medicine, LSU Medical Center, Shreveport 71130-3932.
Alvarez
X
X
Holcombe
R F
RF
D000911:Antibodies, Monoclonal; D001943:Breast Neoplasms / Q000276:immunology*; D015179:Colorectal Neoplasms / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000187:drug effects* / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007978:Levamisole / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D007978:Levamisole