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目的研究选择性环氧化酶-2抑制剂塞来昔布联合替吉奥对胃癌裸鼠皮下移植瘤生长的影响及可能机制。方法建立胃癌裸鼠皮下移植瘤模型,成瘤后将裸鼠随机分为阴性对照组、塞来昔布组、替吉奥组、塞来昔布联合替吉奥组,连续给药21 d后,取材,测量肿瘤体积、计算抑瘤率,TUNEL检测肿瘤组织的凋亡率,免疫组化检测各组PCNA、Bcl-2、caspase-3的表达情况。结果塞来昔布组、替吉奥组、联合给药组的抑瘤率分别为30.8%、50.1%、78.8%。各干预组较对照组凋亡率明显增加(P<0.01),联合给药组较单药组凋亡率明显增加(P<0.01)。各干预组PCNA、Bcl-2的表达较对照组明显降低(P<0.01),联合给药组较单药组明显降低(P<0.05)。各干预组caspase-3的表达较对照组明显升高(P<0.05),联合给药组表达较单药组明显升高(P<0.01)。结论塞来昔布、替吉奥均有明显的抗肿瘤作用,二者联合表现为协同作用,可能是抑制肿瘤细胞的增殖、促进凋亡所致。
Objective To investigate the effect of selective cyclooxygenase-2 inhibitor celecoxib combined with tiagil on the growth of subcutaneous xenografts in nude mice and its possible mechanism. Methods A subcutaneous xenograft model of gastric cancer in nude mice was established. After the tumor was established, nude mice were randomly divided into negative control group, celecoxib group, tegaserod group and celecoxib combined with replacement group. After 21 days of continuous administration The tumor volume was measured and the tumor inhibition rate was calculated. The apoptosis rate of tumor tissue was detected by TUNEL. The expression of PCNA, Bcl-2 and caspase-3 in each group was detected by immunohistochemistry. Results The tumor inhibition rates of celecoxib group, treatment group and combination group were 30.8%, 50.1% and 78.8% respectively. Compared with the control group, the apoptosis rate of each intervention group was significantly increased (P <0.01), and the apoptosis rate of the combination group was significantly higher than that of the control group (P <0.01). The expression of PCNA and Bcl-2 in each intervention group was significantly lower than that in the control group (P <0.01). The combined treatment group was significantly lower than the single drug group (P <0.05). The expression of caspase-3 in each intervention group was significantly higher than that in the control group (P <0.05). The expression of caspase-3 in the combination group was significantly higher than that in the control group (P <0.01). Conclusion Celecoxib and Teguogine have obvious anti-tumor effects, and the combination of the two shows synergistic effects, which may be due to the inhibition of the proliferation of tumor cells and the promotion of apoptosis.