Manganese superoxide dismutase expression correlates with chemosensitivity in human gastric cancer cell lines.
OBJECTIVE
The purpose is to investigate the potential correlation between antioxidant enzyme (AOE) levels and resistance to anticancer drugs in human gastric carcinoma cell lines.


METHODS
Protein contents of AOEs such as manganese superoxide dismutase (MnSOD), copper/zinc superoxide dismutase, catalase, glutathione S-transferase-pi, p-glycoprotein, and multidrug resistance-associated protein were observed by Western blot analysis, and MnSOD activity was measured in six Korean gastric cancer cell lines. The direct correlation between AOEs and the chemosensitivity to doxorubicin (DOX), mitomycin C, 5-fluorouracil, and vinblastine was analyzed by cytotoxicity test. MnSOD was overexpressed by transient transfection of human MnSOD cDNA.


RESULTS
Expressions of AOEs in gastric cancer cell lines were variable. MnSOD expression was related with the resistance to DOX and mitomycin C but not with that to 5-fluorouracil and vinblastine. In comparison, expressions of other AOEs, p-glycoprotein and multidrug resistance-associated protein, were not correlated with tumor sensitivity to any of the drugs used. Cell lines with a high MnSOD protein content showed higher MnSOD activity than those with a low MnSOD protein content. In addition, MnSOD overexpression increased the resistance of gastric carcinoma cells to DOX.


CONCLUSIONS
MnSOD is an important factor of drug response to reactive oxygen species-generating anticancer drugs in the gastric cancer cells. Thus, measurement of MnSOD levels in clinical samples may provide an indication of subsequent treatment response of gastric cancer patients.
Hur
Gwong-Cheung
GC
Department of Anatomy, Cancer Research Institute, College of Medicine, Seoul National University, Seoul, Korea.
Cho
Sung Jin
SJ
Kim
Chan-Hyung
CH
Kim
Min Kyu
MK
Bae
Soo In
SI
Nam
Seon Young
SY
Park
Jong-Wan
JW
Kim
Woo Ho
WH
Lee
Byung Lan
BL
D000970:Antineoplastic Agents / Q000633:toxicity*; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D006861:Hydrogen Peroxide / Q000032:analysis; D007723:Korea; D013274:Stomach Neoplasms / Q000473:pathology*; D013482:Superoxide Dismutase / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism
D000970:Antineoplastic Agents; D006861:Hydrogen Peroxide; D013482:Superoxide Dismutase