白桦酯醇对卵巢癌裸鼠皮下移植瘤组织中MMP-2和MMP-9表达的影响及意义

目的 探讨白桦酯醇对卵巢癌SKOV3细胞裸鼠皮下移植瘤组织中基质金属蛋白酶-2（MMP-2）和基质金属蛋白酶-9（MMP-9）表达的影响和意义。方法 建立卵巢癌SKOV3细胞裸鼠移植瘤模型，将30只裸鼠随机分为白桦酯醇高剂量组（80mg／kg）、中剂量组（40mg／kg）、低剂量组（20mg／kg）以及对照组（生理盐水）和紫杉醇组（135mg／m2），每组6只，腹腔给药02ml/只，隔日1次，连续21d。停药后第2d处死裸鼠，测量其移植瘤体积和瘤重；用免疫组织化学法检测移植瘤组织中MMP-2和MMP-9蛋白的表达并计算表达率。结果 白桦酯醇处理组和紫杉醇组的移植瘤体积和瘤重均小于对照组（P＜0.05）；白桦酯醇中、高剂量组的抑瘤率分别为44.5％和51.4％，均高于其低剂量组的17.5%（P＜0.05）。与对照组比较，白桦酯醇处理组和紫杉醇组移植瘤组织中MMP-2和MMP-9蛋白表达水平均减弱；白桦酯醇低、中、高剂量组移植瘤组织中MMP-2和MMP-9蛋白的表达率（％）分别为47.13±8.67和53.82±7.41、38.29±4.37和48.79±4.63、26.88±5.12和38.93±2.82，均低于对照组的56.78±6.42和69.35±5.03，且白桦酯醇3组之间的差异均有统计学意义（P＜0.05）。结论 白桦酯醇对卵巢癌SKOV3细胞皮下移植瘤的生长有抑制作用，其机制可能与下调MMP-2和MMP-9蛋白的表达有关。

Effects of betulin on the expression of MMP-2 and MMP-9 in tumor tissues of nude mice bearing human ovarian cancer xenograft and their signficance

Objective To investigate the effects of betulin on the expression of matrix metalloproteinase-2 （MMP-2） and matrix metalloproteinase（ MMP-9 ） in tumor tissues of nude mice bearing human ovarian cancer xenograft and their significance. Methods The subcutaneous ovarian cancer SKOV3 xenograft model was successfully established in nude mice. Thirty nude mice were random- ly divided into 5 groups（ n = 6） ： betulin high-dose group（80mg/kg）, betulin medium-dose group（40mg/kg） , betulin low-dose group （20mg/kg）, control group（ normal saline） and paclitaxel group（135mg/m^2）. All the mice received intraperitoneal injection once every two days for 21 days at a dose of 0. 2ml. Then all the mice were sacrificed; the transplantated tumor mass and volume were measured to calculate the tumor inhibitory rate. The protein expression of MMP-2 and MMP-9 were deteced by immunohistochemical method. Results Tumor volumes and masses of mice treated with betulin and taxol were smaller than those of control group when mice were sacrificed（P 〈0. 05）. The tumor inhibitory rate of betulin low-dose group was 17.5% ,lower than 44. 5% and 51.4% in mediumand high-dose group（P 〈0. 05）. The expression of MMP-2 and MMP-9 in eontrol group were （56. 78±6. 42）% and （69.35 ±5.03） %, higher than （47. 13 ±8.67） % and （53.82±7.41 ） % of betulin low-dose group, （38.29±4. 37） % and （48. 79±d. 63 ） % of betulin medium-dose group, and （26. 88±5.12） % and （ 38.93±2. 82 ） % of betulin high-dose group （ P 〈 O. 05 ） ; the expression of the two proteins in the three betulin groups had significance （P 〈 O. 05 ）. Conclusion The betulin can inhibit the growth of transplanted tumors of ovarian cancer SKOV3 cells in nude mice, which may related to the downregulation of the expression of MMP-2 and MMP-9.