Effect of nitric oxide on the proliferation of AGS gastric cancer cells.
OBJECTIVE
Nitric oxide (NO) is involved in many physiologic and pathologic processes. As an important biologic mediator, NO has been the focus of cancer study for its function in tumorigenesis, tumor progression, and death. This study investigated the effect of NO donor sodium nitroprusside (SNP) on the growth and proliferation of gastric cancer cell line AGS.


METHODS
The growth inhibition of AGS cells was analyzed using MTT assay. The cell cycle was measured using flow cytometry. The changes of mRNA expression of proliferating cell nuclear antigen (PCNA) and caspase-3 were examined using reverse transcriptase polymerase chain reaction (RT-PCR), and the protein expressions of PCNA and caspase-3 were analyzed using Western blot.


RESULTS
Dose-dependent SNP inhibited cell growth and proliferation. When the AGS cells were treated with SNP at 100, 500, 1000, 1500, and 2000 mumol/L for 24 h, the growth inhibition rates were (2.02 +/- 2.96)%, (10.82 +/- 2.21)%, (18.95 +/- 3.35)%, (26.88 +/- 2.54)%, and (42.57 +/- 1.27)%, respectively (P < 0.05). SNP altered the cell cycle in AGS cells. Compared with the control group, treatment with SNP at 100, 500, 1000, 1500, and 2000 mumol/L for 24 h reduced the number of cells in the S phase by 2.29%, 7.8%, 11.34%, 20.49%, and 23.6%, respectively, and enhanced the number of cells in the G1/G0 phases by 3.33%, 9.3%, 13.46%, 21.37%, and 24.73%, respectively (P < 0.05). With the increasing concentration and action time of SNP, the expressions of PCNA mRNA and protein decreased. The expression of caspase-3 mRNA remained unchanged, but procaspase-3 was activated.


CONCLUSIONS
NO not only inhibits cell growth and proliferation, but also induces apoptosis in gastric cancer cells, and such effects of NO showed significant dose-dependent activity.
Sang
Jian-Rong
JR
Department of Physiology, Jiangsu University, Zhenjiang, Jiangsu 212013, PR China. sangjianrong@yahoo.com.cn
Chen
Yong-Chang
YC
Shao
Gen-Bao
GB
Huang
Xiao-Jia
XJ
D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D009599:Nitroprusside / Q000494:pharmacology*; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D013274:Stomach Neoplasms / Q000378:metabolism / Q000473:pathology*
D020030:Nitric Oxide Donors; D018809:Proliferating Cell Nuclear Antigen; D012333:RNA, Messenger; D009599:Nitroprusside; C505407:CASP3 protein, human; D053148:Caspase 3