三叶青黄酮对荷Lewis肺癌小鼠脾脏单个核细胞PGE2、COX-2表达的影响

Effect of Flavonoid Extract from Radix Tetrastigme on PGE2 and COX-2 in Spleen Mononuclear Cells of Lewis Lung Carcinoma Mice

目的研究三叶青黄酮对荷Lewis肺癌小鼠脾脏单个核细胞前列腺素E2(PGE2)、环氧化酶-2(COX-2)表达的影响。方法皮下接种法建立Lewis肺癌小鼠动物模型,接种14天后取脾脏,分离单个核细胞培养,以转化生长因子β1(TGF-β1)刺激为模型组,塞来昔布(SC58635)为阳性对照,设三叶青黄酮低、中、高浓度组,无TGF-β1及药物为空白对照组。ELISA法测定单个核细胞分泌PGE2、COX-2浓度。结果 TGF-β1刺激24h后,与空白对照组PGE2(99.31±3.82)pg/m L、COX-2(290.49±5.37)pg/m L比较,其余五组PGE2、COX-2均明显升高,差异有统计学意义(P<0.01)。模型组脾脏单个核细胞体外分泌PGE2[(138.18±4.00)pg/m L]、COX-2[(331.58±5.78)pg/m L]含量最高。与模型组比较,给药组PGE2、COX-2含量均明显下降,差异有统计学意义(P<0.01)。PGE2含量依次为塞来昔布组(110.13±2.38)pg/m L<三叶青黄酮高剂量组(118.18±1.96)pg/m L<中剂量组(121.62±4.44)pg/m L<低剂量组(128.90±4.24)pg/m L。COX-2含量依次为塞来昔布组(309.51±2.85)pg/m L<三叶青黄酮高剂量组(319.64±2.29)pg/m L<中剂量组(323.92±2.61)pg/m L<低剂量组(327.07±4.53)pg/m L。给药组组间差异有统计学意义(P<0.05,P<0.01)。结论三叶青黄酮在体外可能通过影响PGE2、COX-2表达水平,改善肿瘤微环境,起到抗肿瘤作用,其作用与剂量呈正比。

Objective To investigate the effect of flavonoid extract of Radix Tetrastigme on the Expression of prostaglandin 2（PGE2） and cyclooxygenase-2（COX-2） in spleen mononuclear cells of mice with lung cancer.Methods Lewis lung carcinoma model was established with subcutaneous inoculation and the spleen was obtained after 14 days to isolate mononuclear cells, than were divided into model group（with TGF-β1 stimulation）, positive group（with celebrex）, low-, medium-, and high-dose flavonoid extract of Radix Tetrastigme groups, and blank group. ELISA was used to determine the contents of PGE2 and COX-2. Results After 24-h TGF-β1 stimulation,compared to blank group（PGE2： 99.31±3.82pg/m L, COX-2： 290.49±5.37pg/m L）, the contents of PGE2 and COX-2in other 5 groups increased with a significant difference（P〈0.01）. The highest level of PGE2 and COX-2 was in model group（138.18±4.00pg/m L and 331.58±5.78pg/m L, respectively）. Compared with model group, the contents of PGE2 and COX-2 in drug groups were significantly reduced（P 0.01）. The PGE2 level in celebrex group and high-, medium-, and low-dose flavonoid extract of Radix Tetrastigme groups were as follows： 110.13 ±2.38pg/m L,118.18±1.96pg/m L, 121.62±4.44pg/m L, and 128.90±4.24pg/m L; the COX-2 level were the following： 309.51±2.85pg/m L, 319.64 ±2.29pg/m L, 323.92 ±2.61pg/m L and 327.07 ±4.53pg/m L; siginifcant difference was found among drug groups（P〈0.05 or P〈0.01）. Conclusion Flavonoid extract of Radix Tetrastigme can improve the tumor microenvironment by regulating the expression of PGE2 and COX-2 to against the tumor in a dose-dependent manner.