Growth inhibition and apoptosis induction of Sulindac on Human gastric cancer cells.
OBJECTIVE
To evaluate the effects of sulindac in inducing growth inhibition and apoptosis of human gastric cancer cells in comparison with human hepatocellular carcinoma (HCC) cells.


METHODS
The human gastric cancer cell lines MKN45 and MKN28 and human hepatocellular carcinoma cell lines HepG(2) and SMMC7721 were used for the study. Anti-proliferative effect was measured by MTT assay, and apoptosis was determined by Hoechst-33258 staining, electronography and DNA fragmentation. The protein of cyclooxygenase-2 (COX-2) and Bcl-2 were detected by Western dot blotting.


RESULTS
Sulindac could initiate growth inhibition and apoptosis of MKN45, MKN28, HepG(2) and SMMC7721 cells in a dose-and time-dependent manner. Growth inhibitory activity and apoptosis were more sensitive in HepG(2) cells than in SMMC7721 cells, MKN45 and MKN28 cells. After 24 hours incubation with sulindac at 2mmol x L(-1) and 4mmol x L(-1), the level of COX-2 and Bcl-2 protein were lowered in MKN45, SMMC7721 and HepG(2) cells but not in MKN28 cells.


CONCLUSIONS
Sulindac could inhibit the growth of gastric cancer cells and HCC cells effectively in vitro by apoptosis induction, which was associated with regression of COX-2 and Bcl-2 expression. The growth inhibition and apoptosis of HCC cells were greater than that of human gastric cancer cells. The different effects of apoptosis in gastric cancer cells may be related to the differentiation of the cells.
Wu
Y L
YL
Department of Gastroenterology, Ruijin Hospital, Shanghai Second Medical University, Shanghai 200025, China. Sunborjxh@yahoo.com.cn
Sun
B
B
Zhang
X J
XJ
Wang
S N
SN
He
H Y
HY
Qiao
M M
MM
Zhong
J
J
Xu
J Y
JY
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D006528:Carcinoma, Hepatocellular / Q000473:pathology / Q000503:physiopathology; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology / Q000503:physiopathology; D013274:Stomach Neoplasms / Q000473:pathology* / Q000503:physiopathology*; D013467:Sulindac / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D013467:Sulindac