Study On Signal Transducer And Activator Of Transcription 3 Signaling Pathway In Mechanism Of Nimesulide Against Gasric Cancer

Objective: To investigate the inhibition effect of proliferation of gastric cancer cell line SGC7901 treated with selective cyclooxgenase 2 (COX-2) inhibitor, nimesulide and the probable mechanism of cell signal transduction in vitro. To observe the influence of nimesulide, nimesulide combined with 5-fluorouracil on growth of human gastric cancer xenograft in nude mice in vivo.Methods: SGC7901 cells were treated with nimesulide in vitro. MTT assay was used to measure the cell proliferation; Flow cytometry was used to detect cell cycle and apoptosis. The expression of P-Stat3, CyclinD1 and Bcl-2 proteins related to Stat3 signaling pathway in SGC-7901 cells were examined by Western blot before and after treatment respectively. The influence of nimesulide, nimesulide combined with 5-fluorouracil on volume and weight of human gastric cancer xenograft in nude mice was observed in vivo.Results: MTT validated that nimesulide inhibited the growth of gastric cancer cells obviously in a time- and dose-dependent manner.The result of Flow cytometry: The percent of apoptosis of gastric cancer cell line SGC7901 treated with nimesulide at 100umol/l,200umol/l for 48 hours rose compared with that of control group; Percent of apoptosis also rose with the increasement of drug concentration at the same time. The proportion of SGC7901 hoisted in G0/G1 phase, little influenced in s phase, decreased in G2/M phase. A great deal of cell treated with nimesulide was arrested in G0/G1 phase in a dose-dependent manner. The result of Western blot: the expression of P-Stat3, CyclinD1, Bcl-2 proteins were decreased in SGC-7901 cells treated with 100umol/l nimesulide for 24 and 48 hours respectively. The result of experiment in vivo: the average tumors'volume and weight of each treatment group reduced obviously compared with that of control group (P<0.05). The average volume and weight of tumors treated with nimesulide combined with 5FU much decreased than 5FU group and nimesulide group (P<0.05). The discrepancy of average volume and weight of tumour between 5FU group and nimesulide group had no significance (P>0.05). Nimesulide could inhibit the growth of gastric cancer xenograft, and the inhibition rate was 52%. The effect of 5FU combined with nimesulide group on inhibiting tumor was strongest and the inhibition rate was 89% that had great difference compared with other groups. The discrepancy of inhibition rate between 5FU group and nimesulide group had no significance (P>0.05). Conclusions: In vitro, nimesulide could inhibit the proliferation of gastric cancer cell line SGC7901; prevent the course of cell cycle; induce apoptosis through down-regulating the expression of P-Stat3, CyclinD1, Bcl-2 proteins, which was probably one of its molecular mechanisms. In vivo, Nimesulide could inhibit the growth of human gastric cancer xenograft in nude mice. The inhibition effect of nimesulide almost was the same as 5-Fu and the inhibition effect of nimesulide combined with 5-Fu boost up obviously.