姜黄素对小鼠宫颈癌皮下移植瘤模型肿瘤标志分子水平及宫颈癌细胞产生一氧化氮能力的影响
|
摘要
目的探究姜黄素对宫颈癌皮下移植瘤模型小鼠肿瘤标志分子水平及宫颈癌细胞产生一氧化氮(NO)能力的影响。方法选取45只雌性C57BL/6小鼠,经皮下注射密度为5×105个/毫升的He La细胞悬液0. 2 m L,构建宫颈癌皮下移植瘤模型,建模1周后,待肿瘤基本形成,将其随机分为3组(每组15只):对照组、实验组、模型组。对照组予以腹腔注射顺铂2 mg·kg~(-1),每2天1次;实验组予以灌胃姜黄素5 g·kg~(-1),每天1次;模型组予以灌胃等量生理盐水,每天1次,各组均连续给药2周。比较各组小鼠病灶体积、病灶质量、血清及肿瘤组织中肿瘤标志分子水平;另以Griess法检测并比较各组肿瘤组织NO浓度,以免疫组化法检测肿瘤组织中诱导型一氧化氮合酶(i NOS)表达情况。结果干预后,模型组、对照组及实验组小鼠肿瘤体积分别为(2. 17±0. 12),(1. 53±0. 11),(1. 64±0. 13) mm~3;肿瘤质量分别为(5. 84±0. 53),(2. 65±0. 46),(5. 01±0. 33) g; NO浓度分别为(20. 63±2. 12),(13. 28±2. 06),(15. 43±2. 09)μmol·L-1; i NOS免疫组化评分分别为(8. 71±3. 25),(5. 04±3. 16),(6. 89±3. 32)分;血清基质金属蛋白酶(MMP)-2分别为(277. 41±7. 65),(153. 45±6. 96)和(199. 87±7. 09)μg·m L~(-1); MMP-9分别为(302. 86±9. 69),(211. 44±10. 14)和(179. 23±9. 87)μg·m L~(-1);血管内皮生长因子(VEGF)分别为(324. 16±10. 54),(178. 64±9. 97)和(132. 11±9. 84)μg·m L~(-1);差异均有统计学意义(P <0. 05或P <0. 01)。结论姜黄素可有效降低宫颈癌皮下移植瘤小鼠血清及肿瘤组织中肿瘤标志分子水平,并抑制肿瘤细胞产生NO。
Objective To explore the effects of curcumin on the tumor marker molecular levels and the ability of cervical cancer cell in producing nitric oxide( NO) of cervical subcutaneous transplantation in mice tumor model. Methods Forty-five female C57 BL/6 mice were selected and bulit cervical subcutaneous transplantation tumor model by subcutaneous injection of 5 × 10~5/m L HeLa cell suspension. One week after modeling,the mice were randomly divided into 3 groups,15 mice in each group: Control group( intraperitioneal injected 2 mg · kg~(-1) cisplatin,1 time/2 d),test group( gavaged 5 g · kg~(-1) curcumin,1 time·d~(-1)) and model group( gavaged equivalent normal saline,1 time·d~(-1)),each group were treated for 2 weeks. The lesion volume and mass,the tumor marker molecular levels of serum and tumor tissue were compared; the NO concentration of tumor tissue in each group were detected and compared by Griess method,and the expression of inducible nitric oxide synthase( i NOS) in tumor tissue were detected by immunohistochemical method. Results After treatment,the lesion volume of model group,control group and test group were( 2. 17 ± 0. 12),( 1. 53 ± 0. 11),( 1. 64 ± 0. 13) mm~3 respectively; the tumor mass were( 5. 84 ± 0. 53),( 2. 65 ± 0. 46),( 5. 01 ± 0. 33) g respectively; the NO concentration were( 20. 63 ± 2. 12),( 13. 28 ± 2. 06),( 15. 43 ± 2. 09) μmol · L~(-1) respectively; the immunohistochemical scores of i NOS were( 8. 71 ± 3. 25),( 5. 04 ± 3. 16),( 6. 89 ± 3. 32) score respectively; the content of serum matrix metalloproteinase-2 were( 277. 41 ± 7. 65),( 153. 45 ± 6. 96),( 199. 87 ± 7. 09) μg·m L~(-1) respectively; the content of serum MMP-9 were( 302. 86 ± 9. 69),( 211. 44 ± 10. 14),( 179. 23 ± 9. 87) μg·m L~(-1) respectively; the content of serum vascular endothelial growth factor( VEGF) were( 324. 16 ± 10. 54),( 178. 64 ± 9. 97),( 132. 11 ± 9. 84) μg·m L~(-1) respectively,and the difference between 3 groups was significant( P < 0. 05 or P < 0. 01). Conclusion Curcumin can reduce the tumor marker molecular levels of cervical subcutaneous transplantation in mice tumor model,and inhibit NO production.
Objective To explore the effects of curcumin on the tumor marker molecular levels and the ability of cervical cancer cell in producing nitric oxide( NO) of cervical subcutaneous transplantation in mice tumor model. Methods Forty-five female C57 BL/6 mice were selected and bulit cervical subcutaneous transplantation tumor model by subcutaneous injection of 5 × 10~5/m L HeLa cell suspension. One week after modeling,the mice were randomly divided into 3 groups,15 mice in each group: Control group( intraperitioneal injected 2 mg · kg~(-1) cisplatin,1 time/2 d),test group( gavaged 5 g · kg~(-1) curcumin,1 time·d~(-1)) and model group( gavaged equivalent normal saline,1 time·d~(-1)),each group were treated for 2 weeks. The lesion volume and mass,the tumor marker molecular levels of serum and tumor tissue were compared; the NO concentration of tumor tissue in each group were detected and compared by Griess method,and the expression of inducible nitric oxide synthase( i NOS) in tumor tissue were detected by immunohistochemical method. Results After treatment,the lesion volume of model group,control group and test group were( 2. 17 ± 0. 12),( 1. 53 ± 0. 11),( 1. 64 ± 0. 13) mm~3 respectively; the tumor mass were( 5. 84 ± 0. 53),( 2. 65 ± 0. 46),( 5. 01 ± 0. 33) g respectively; the NO concentration were( 20. 63 ± 2. 12),( 13. 28 ± 2. 06),( 15. 43 ± 2. 09) μmol · L~(-1) respectively; the immunohistochemical scores of i NOS were( 8. 71 ± 3. 25),( 5. 04 ± 3. 16),( 6. 89 ± 3. 32) score respectively; the content of serum matrix metalloproteinase-2 were( 277. 41 ± 7. 65),( 153. 45 ± 6. 96),( 199. 87 ± 7. 09) μg·m L~(-1) respectively; the content of serum MMP-9 were( 302. 86 ± 9. 69),( 211. 44 ± 10. 14),( 179. 23 ± 9. 87) μg·m L~(-1) respectively; the content of serum vascular endothelial growth factor( VEGF) were( 324. 16 ± 10. 54),( 178. 64 ± 9. 97),( 132. 11 ± 9. 84) μg·m L~(-1) respectively,and the difference between 3 groups was significant( P < 0. 05 or P < 0. 01). Conclusion Curcumin can reduce the tumor marker molecular levels of cervical subcutaneous transplantation in mice tumor model,and inhibit NO production.
引文
[1]黄果,王佑权,谭米多,等.姜黄素抗肿瘤作用机制的研究进展[J].肿瘤药学,2014,4(5):328-330.
[2]GONG C,DENG S,WU Q,et al.Improving antiangiogenesis and anti-tumor activity of curcumin by biodegradable polymeric micelles[J].Biomaterials,2013,34(4):1413-1419.
[3]张凯举,赵艳忠,尚宏伟,等.BALB/c裸小鼠人宫颈癌模型的建立[J].首都医科大学学报,2008,29(5):593-596.
[4]范海丽,史恩祥,王伟,等.酶联免疫吸附试验检测过程中的质量控制[J].解放军医药杂志,2011,23(5):51-53.
[5]YUCEL A A,GULEN S,DINCER S,et al.Comparison of two different applications of the Griess method for nitric oxide measurement[J].J Exp Int Med,2012,2(2):167-171.
[6]王文勇,黄晓峰,王映梅,等.免疫组化技术标准化的探讨[J].细胞与分子免疫学杂志,2011,27(8):927-929.
[2]GONG C,DENG S,WU Q,et al.Improving antiangiogenesis and anti-tumor activity of curcumin by biodegradable polymeric micelles[J].Biomaterials,2013,34(4):1413-1419.
[3]张凯举,赵艳忠,尚宏伟,等.BALB/c裸小鼠人宫颈癌模型的建立[J].首都医科大学学报,2008,29(5):593-596.
[4]范海丽,史恩祥,王伟,等.酶联免疫吸附试验检测过程中的质量控制[J].解放军医药杂志,2011,23(5):51-53.
[5]YUCEL A A,GULEN S,DINCER S,et al.Comparison of two different applications of the Griess method for nitric oxide measurement[J].J Exp Int Med,2012,2(2):167-171.
[6]王文勇,黄晓峰,王映梅,等.免疫组化技术标准化的探讨[J].细胞与分子免疫学杂志,2011,27(8):927-929.