Apoptosis of human gastric cancer SGC-7901 cells induced by mitomycin combined with sulindac.
OBJECTIVE
To investigate the effects of mitomycin (MMC) combined with sulindac on cell viability, apoptotic induction and expression of apoptosis-related gene Bcl-2 and cyclooxygenase-2 (COX-2) in gastric cancer SGC-7901 cells.


METHODS
Human gastric cancer SGC-7901 cells were divided into three treatment groups,namely sulindac treatment group, MMC treatment group and combined sulindac with MMC treatment group. After being treated with drugs, cell viability was examined by MTT assay. Flow cytometry was used to evaluate the cell cycle distribution and apoptotic rates. Morphology of the cells was observed under light microscope and interactive laser microscope. Expression of COX-2 and Bcl-2 was determined by immunocytochemical method.


RESULTS
After exposure for 12 h to three kinds of drugs, gastric cancer SGC-7901 cells presented some morphological features of apoptosis, including cell shrinkage, nuclear condensation, DNA fragmentation and formation of apoptotic bodies. Growth inhibition was more obvious in combined sulindac with MMC treatment group and sulindac treatment group than in MMC treatment group. The apoptotic rates in co-treated cells and MMC-treated cells 24 h after treatment were 12.0% and 7.2%, respectively. After exposure for 24 h to MMC, the expression of COX-2 and Bcl-2 protein was up-regulated, COX-2 levels were down-regulated but Bcl-2 gene expression was not changed significantly in combined treatment group.


CONCLUSIONS
MMC-induced apoptosis is reduced by up-regulating the expression of COX-2 and Bcl-2 genes. MMC combined with sulindac can suppress the growth of gastric cancer cells through induction of apoptosis mediated by down-regulation of apoptosis-related Bcl-2 and COX-2 gene.
Ma
Li
L
Department of Gastroenterology, Second Affiliated Hospital, Lanzhou Medical University, Lanzhou 730000, Gansu Province, China. malilucky007@sina.com
Xie
Yong-Le
YL
Yu
Yi
Y
Zhang
Qiu-Ning
QN
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D051546:Cyclooxygenase 2; D004359:Drug Therapy, Combination; D016193:G1 Phase / Q000187:drug effects; D006801:Humans; D008565:Membrane Proteins; D016685:Mitomycin / Q000494:pharmacology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology; D013467:Sulindac / Q000494:pharmacology*
D000903:Antibiotics, Antineoplastic; D000970:Antineoplastic Agents; D008565:Membrane Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D013467:Sulindac; D016685:Mitomycin; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases