Malignant ascites increases the antioxidant ability of human ovarian (SKOV-3) and gastric adenocarcinoma (KATO-III) cells.
OBJECTIVE
The antioxidant status of cancer cells is an important factor in tumor invasion and metastases. This study investigated whether metastatic cancer cells derive beneficial antioxidant protection from ascitic fluid and are rendered resistant to oxidative stress in the form of a chemically generated free radical insult.


METHODS
Human gastric carcinoma (KATO-III) and ovarian adenocarcinoma (SKOV-3) cell lines were cultured and incubated for 24 h with (1) M199 medium; (2) M199 + 20% fetal calf serum (FCS); (3) malignant ascites. All cells were exposed to a hydroxyl radical-generating system for 1 h. Cellular lipid peroxidation was assessed by measuring malondialdehyde (MDA) in cell suspensions. Glutathione (GSH) levels in cell pellet were measured in SKOV-3 cells after 0, 24, 48, and 72 h of incubation with buthionine sulphoximine (BSO). CD44 gene expression of cancer cells was analyzed by Northern blotting.


RESULTS
The results showed that the cancer cells were rendered resistant to oxidative stress and with upregulated CD44 gene expression by components of malignant ascites.


CONCLUSIONS
These findings suggest that malignant ascites increases the antioxidant ability of cancer cells and the potential of adhesion and invasion. Thus, determination of the nature of these putative tumor-protective components of ascites may provide targets for therapeutic intervention.
Yang
Wenxuan
W
University Department of Surgery, Royal Free and University College Medical School, University College London and The Royal Free Hospital, Pond Street, London NW3 2QG, UK.
Toffa
Samuel E
SE
Lohn
Jonathan W G
JW
Seifalian
Alexander M
AM
Winslet
Marc C
MC
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000975:Antioxidants / Q000378:metabolism*; D001201:Ascites / Q000378:metabolism* / Q000473:pathology; D015152:Blotting, Northern; D019328:Buthionine Sulfoximine / Q000494:pharmacology; D002448:Cell Adhesion / Q000502:physiology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D015870:Gene Expression; D005978:Glutathione / Q000172:deficiency / Q000378:metabolism; D006801:Humans; D018960:Hyaluronan Receptors / Q000096:biosynthesis / Q000235:genetics; D015227:Lipid Peroxidation; D008315:Malondialdehyde / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
D000975:Antioxidants; D018960:Hyaluronan Receptors; D008315:Malondialdehyde; D019328:Buthionine Sulfoximine; D005978:Glutathione