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15-脱氧前列腺素J2对胃癌生长影响及机制的体内研究

Effect of PPARγ Ligands 15d-PGJ2 on Gastric Cancer Growth and Its Mechanism in vivo

  • 摘要: 目的 探讨过氧化物酶体增殖物激活受体gamma(PPARγ)的天然配体15-脱氧前列腺素J2(15d-PGJ2 )在体内对人胃癌细胞生长的作用以及对survivin、p27、Skp2和CD44表达的影响。方法 将人胃癌MGC803细胞,注射在12只裸鼠右上肢肩背部皮下。待长出肉眼可见的肿瘤时,将12只裸鼠随机分为实验组和对照组,每组6只。实验组静脉给予15d-PGJ2,对照组静脉给予PBS。应用反转录聚合酶链反应(RT-PCR)和Western blot方法分别检测皮下移植瘤组织中survivin、Skp2、p27的 mRNA及蛋白的表达。应用免疫组织化学法检测瘤组织CD44的表达,并对阳性细胞进行计数。结果 (1)给予15d-PGJ2 16次后,实验组裸鼠移植瘤平均体积(573.86±242.90)mm3明显小于对照组裸鼠移植瘤平均体积(1206.46±272.22) mm3(P<0.05)。(2)实验组与对照组相比,瘤组织survivin 和Skp2的mRNA及蛋白质低表达而p27 mRNA及蛋白质高表达。(3) CD44阳性细胞率,实验组 (51.20±12.45)%明显少于对照组 (85.45±15.45)% (P<0.05)。结论 15d-PGJ2能抑制人胃癌细胞的生长,调节survivin 、p27、Skp2和CD44的表达,提示15d-PGJ2有可能对治疗胃癌有效。

     

    Abstract: Objective To investigate whether 15-deoxy prostaglandin J2 (15d-PGJ2), natural ligand of peroxisome proliferator-activation gamma (PPARγ) receptor, inhibit the growth of human gastric cancer cell and its regulation on the expressions of p27, Skp2, survivin and CD44 in vivo. Methods Human gastric carcinoma MGC803 cells were injected into upper body of right upper limb of 12 nude mice subcutaneously. When small nodules grew, all nude mice were divided into control and experimental group (n= 6) randomly. Control group were given PBS, while the experimental group were given intravenous injection of 15d-PGJ2 every day. Reverse transcription polymerase chain reaction (RT-PCR) and Western blot were used to detect the expressions of p27, Skp2, survivin mRNA and protein in subcutaneously xenografted tumor tissues. Immunohistochemical staining was used to detect CD44 expression and for count the number of CD44-positive cells. Results After 15d-PGJ2 was given for 16 times, the average tumor volume of experimental group(573.86±242.90) mm3, was significantly smaller than that of control group(1244.01±257.81) mm3(P <0.05). The expressions of p27 mRNA and protein in experimental group were much higher than those in control group, while the expressions of Skp2, survivin mRNA and protein in experimental group were lower than those in control group. The rate of CD44 positive cells in experimental group(51.20±12.45)%, was significantly lower than that of control group(85.45±15.45)% (P<0.05). Conclusion 15d-PGJ2 inhibits the growth of human gastric cancer cells and regulates the expressions of p27, Skp2, survivin and CD44 suggesting that 15d-PGJ2 may be effective for treatment of gastric cancer.

     

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