姜黄素对宫颈癌大鼠的影响及作用机制研究

Study on effect of curcumin on cervical cancer model rats and its mechanism

目的研究姜黄素对宫颈癌大鼠的影响及作用机制。方法用人宫颈癌HeLa细胞悬液在大鼠左侧腋窝处皮下注射建立宫颈癌模型;空白组予以0. 9%Na Cl左侧腋窝处皮下注射。按照体重将造模成功大鼠随机分为5组:模型组、对照组和低、中、高3个剂量实验组,每组13只。模型组和空白组均腹腔注射0. 9%NaCl 1. 25 mL·kg-1;对照组腹腔注射16 mg·m L-1氟尿嘧啶溶液1. 25mL·kg-1;低、中、高3个剂量实验组分别腹腔注射48,96,192 mg·mL-1姜黄素溶液1. 25 m L·kg-1,均隔日给药1次,连续20 d。用免疫组化法检测肿瘤组织微血管密度(MVD),用实时荧光定量聚合酶链反应检测肿瘤组织微小核糖核酸-21(miR-21)和信号转导及转录活化因子-3 (Stat-3)的基因表达水平。结果空白组、模型组、对照组和低、中、高3个剂量实验组的MVD分别为(6. 26±0. 72),(23. 18±3. 04),(10. 25±1. 21),(17. 15±2. 33),(13. 84±1. 58)和(10. 62±1. 36)个;上述6组的miR-21表达水平(2-ΔΔCt值)分别为0. 44±0. 06,1. 13±0. 15,0. 63±0. 06,1. 03±0. 12,0. 87±0. 09和0. 64±0. 07;上述6组的Stat-3表达水平(2-ΔΔCt值)分别为0. 19±0. 02,0. 67±0. 09,0. 26±0. 03,0. 54±0. 07,0. 42±0. 06和0. 28±0. 04;模型组与空白组相比,上述指标的差异均有统计学意义(均P <0. 05),对照组和低、中、高3个剂量实验组与模型组相比,上述指标的差异均有统计学意义(均P <0. 05)。结论姜黄素能明显抑制宫颈癌大鼠肿瘤生长,抑制肿瘤组织的miR-21、Stat-3基因的表达水平,且药物浓度越高作用效果越明显。

Objective To analyze the effect of curcumin on cervical cancer model rats and its mechanism.Methods The rats were randomly divided into blank group and model building group.The model building group was established cervical cancer model by subcutaneous injection of human cervical cancer HeLa cell suspension into the left axilla;rats in the blank group received subcutaneous injection of physiological saline into the left axilla.Successful model of rats were randomly divided into five groups:model group,control group and low,midddle and high doses experimental groups,with 13 rats in each group.The model group and blank group were given physiological saline solution 1.25 mL·kg-1 by intraperitoneal injection,control group was given 16 mg·mL-1 fluorouracil solution 1.25 mL·kg-1 by intraperitoneal injection,three doses experimental groups were given 48,96,192 mg·mL-1 curcumin solution1.25 mL·kg-1 by intraperitoneal injection;1 time every other day for 20 days.Microvessel density(MVD)of tumor tissue was detected by immunohistochemistry.The expression levels of micro ribonucleic acid-21(microRNA-21)mRNA,signal transducer and activator of transcription-3(Stat-3)mRNA in tumor tissues was detected by real-time fluorescence quantitative polymerase chain reaction.Results MVD in blank group,model group,control group and low,middle and high doses experimental groups were respectively(6.26±0.72),(23.18±3.04),(10.25±1.21),(17.15±2.33),(13.84±1.58),(10.62±1.36)microvessels;the expression level of miRNA-21(2-ΔΔCt values)in the above six groups were respectively 0.44±0.06,1.13±0.15,0.63±0.06,1.03±0.12,0.87±0.09,0.64±0.07;the expression level of Stat-3(2-ΔΔCt values)in the above six groups were respectively 0.19±0.02,0.67±0.09,0.26±0.03,0.54±0.07,0.42±0.06,0.28±0.04.Comparing between model group with blank group,the difference of the factors were significant(all P<0.05);comparing between control group and three doses experimental groups with model group,the difference of the factors were all significant(all P<0.05).Conclusion Curcumin can significantly inhi-bit the growth of cervical cancer in rats model,inhibit the expression of miR-21 and Stat-3 in tumor tissues,and the higher the drug dose is,the more obvious the effect is.