A molecular biological study of anti-tumor mechanisms of an anti-cancer agent Oxaliplatin against established human gastric cancer cell lines.
We report that preoperative administration of Oxaliplatin, a new anti-cancer platinum agent, is an effective treatment for gastric cancer. The purpose of this in vitro study is to determine whether Oxaliplatin induces apoptosis in established human gastric cancer cell lines. Five established gastric cancer cell lines are used: MNK45, KATO-III, OKAJIMA, MNK28 and MNK74. Chemosensitivity to l-OHP is studied using a growth inhibition test. Induction of apoptosis in gastric cancer cells is analyzed by assessing DNA ladder formation, DNA fragmentation and actin cleavage. While all five gastric cancer cell lines are sensitive to Oxaliplatin, the poorly differentiated lines are the most sensitive. DNA ladder formation and/or DNA fragmentation are detected in all gastric cancer cell lines. However, actin cleavage is not detected in any of the cell lines. Oxaliplatin has an anti-cancer effect on human gastric cancer cell lines, particularly cell lines of poorly differentiated adenocarcinoma, indicating that Oxaliplatin would be an effective treatment for poorly differentiated gastric cancer. Oxaliplatin induces apoptosis in gastric cancer cell lines, but actin cleavage is not detected in cancer cells. This finding suggests that (1) the apoptotic caspase pathway leads mainly to DNA condensation and fragmentation, and (2) caspase-independent apoptotic pathways may be activated when gastric cancer cells are treated with Oxaliplatin.
Eriguchi
M
M
Department of Surgery, Institute of Medical Science, University of Tokyo, Tokyo, Japan. eriguchi@ip.rcast.u-tokyo.jp
Nonaka
Y
Y
Yanagie
H
H
Yoshizaki
I
I
Takeda
Y
Y
Sekiguchi
M
M
D000199:Actins / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D020169:Caspases / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D053938:DNA Fragmentation; D006801:Humans; D015151:Immunoblotting; D009944:Organoplatinum Compounds / Q000494:pharmacology*; D000077150:Oxaliplatin; D013274:Stomach Neoplasms
D000199:Actins; D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D020169:Caspases