| Object: COX enzymes catalyze the synthesis of prostaglandins (PGs) from arachidonic acid. The two isoforms of COX, COX-1 and COX-2, differ in many respects. COX-1 is expressed constitutively in most tissues and appears to be responsible for the production of PGs that control normal physiological function. COX-2 is induced by mitogenic and inflammatory stimuli, which results in enhanced synthesis of PGs which have been widely implicated in tumor growth. COX-2 affects many processes that have been implicated in different stages of carcinogenesis, including xenobiotic metabolism, angiogenesis, apoptosis, immune function and tumor invasiveness. Inhibitors of COX is associated with a reduced risk of several malignancies, including colorectal cancer. Ursolic acid(UA) is the major anti-tumor constituents of many Chinese traditional drugs. Much focus has been placed on its antimutagenic, antitumor and antioxidation effects. Furthermore, UA exhibited cytotoxicity and apoptosis effect toward digestive tract tumor and leukemia cells. In addition, some investigations show that UA suppresses the activation of COX-2 gene, provide a mechanistic basis for the chemopreventive and anti-inflammatory properties of UA. Here, we investigated the effects of UA on the growth and apoptosis of human gastric cancer cells SGC-7901 which high express COX-2 protein.Methods: Human gastric cancer cells SGC-7901 were cultured by RPMI-1640. The concentrations of UA were 20, 30, 40, 50 μmol/L and the time points of cell culture were 12, 24, 36, 48 h. The anti-proliferation effect of UA towards SGC-7901 and effect of exogenous PGE2 on cell proliferation were determined by MTT assay; The effect on cell cycle and apoptosis was analyzed by flow cytometry; Western blot assay was used to determined expression of COX-2, Bcl-2 and Bax protein; The effect of UA on PGE2 production in SGC-7901 cells was determined by radioimmunoassay(RI A).Results: UA could inhibit the cells proliferation in a time-response and concentration-response ways; This role could not be invert in the presence ofexogenously added PGE2; The cell percent of G0/G1 phase increased and somewhat in S phase, but G2 phase had not markedly changed after treatment; The ratio of apoptosis was increased; COX-2 protein level was decreased by UA in a concentration-dependent manner; PGE2 production was inhibited, whereas there has no concentration-dependent effect; Bcl-2 protein was decreased in a concentration-dependent manner, but Bax was not changed.Conclusion: UA markedly reduced SGC-7901 cell growth in a dose- and time-dependent manner and then induced subsequent apoptosis, this response was accompanied with a increase in the G1 phase. COX-2 pathway plays an important role in inhibitory effect of UA. UA led to a inhibition of PGE2 which indicated that UA exhibited its antiproliferation and antitumor effects by inhibited COX-2 enzyme activity. Exogenous PGE2 failed to affect the response of cells to UA, suggesting the anti-proliferation effect of UA partially dependent on inhibition of COX-2 pathway. The level of Bcl-2 protein decreased indicating that UA increased the sensitivity of cells to apoptosis. Apoptosis induced by UA is increased, which may be caused by down-regulating the expression of COX-2 and Bcl-2. Our findings suggest a possible mechanism for chemopreventive and anti-tumor effects of UA.
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