|
|
- 2016
辣椒素通过下调COX-2和mPGES-1抑制IL-1β诱导的NCI-H460细胞PGE？？2含量的实验研究
|
Abstract:
摘要：目的 观察辣椒素对IL-1β诱导的人肺腺癌NCI-H460细胞PGE2含量的影响，并且进一步观察其对COX-2和mPGES-1的影响，探讨其抗非小细胞肺癌(NSCLC)的可能机制。方法 体外培养NCI-H460细胞，采用MTT比色分析法，观察辣椒素对NCI-H460细胞增殖抑制作用，计算IC50；采用IL-1β刺激的方法构建炎症模型，ELISA法检测辣椒素对NCI-H460细胞PGE2含量和COX-2活性的影响；Western blot法检测辣椒素对NCI-H460细胞COX-2、mPGES-1蛋白表达的影响；Real-time PCR法检测辣椒素对NCI-H460细胞COX-2 mRNA和mPGES-1 mRNA表达的影响。结果 MTT比色分析结果表明，辣椒素对NCI-H460细胞增殖具有明显抑制作用，与对照组比较，差异具有统计学意义(P<0.05或P<0.01)。辣椒素明显降低NCI-H460细胞COX-2活性和PGE2浓度，而且明显降低NCI-H460细胞COX-2、mPGES-1蛋白及其mRNA的表达，且呈剂量依赖性，与模型组比较，差异具有统计学意义(P<0.05)。结论 辣椒素通过降低NCI-H460细胞COX-2和mPGES-1 mRNA表达从而抑制PGE2释放，可能是其抗NSCLC的机制之一。
ABSTRACT: Objective To observe the effects of capsaicin on PGE2 concentration of IL-1β-induced human large cell carcinoma NCI-H460 cells, and further observe its effect on COX-2 and mPGES-1 so as to explore the possible mechanisms against non-small cell lung cancer. Methods NCI-H460 cells were cultured in vitro; the effect of capsaicin in inhibiting NCI-H460 cells proliferation was observed. The 50% inhibitory concentration (IC50) was measured by MTT assay. IL-1β stimulation method was used to construct inflammation model, and the effects of capsaicin on COX-2 activity and PGE2 concentration in NCI-H460 cells were measured by ELISA. The effects of capsaicin on COX-2 and mPGES-1 protein level in NCI-H460 cells were analyzed by Western blot; the effects of capsaicin on COX-2 mRNA and mPGES-1 mRNA expressions in NCI-H460 cells were analyzed by Real-time PCR. Results MTT assay results showed that the growth of NCI-H460 cells treated with capsaicin was significantly inhibited compared with the control group (P<0.05 or P<0.01). Capsaicin could significantly decrease COX-2 activity and PGE2 concentration in NCI-H460 cells, and significantly decrease COX-2, mPGES-1 protein levels as well as COX-2, mPGES-1 mRNA expressions in NCI-H460 cells in a dose-dependent manner compared with the control group (P<0.05). Conclusion Capsaicin inhibits the release of PGE2 by downregulating COX-2 and mPGES-1 mRNA expressions in NCI-H460 cells, which may be one mechanism of its effect against non-small cell lung cancer
| [1] | 付艳丽，屠洪斌，董志毅，等. 原发性肺癌中医证型与TNM分期及肿瘤抗原相关性研究[J]. 世界科学技术-中医药现代化, 2015, 17(6):1210-1214. |
| [2] | 田芳，江亚南，张晓艳，等. 辣椒素对食管鳞状细胞癌细胞凋亡和NF-кB信号通路相关蛋白表达的影响[J]. 郑州大学学报(医学版), 2013, 48(4):437-440. |
| [3] | 倪力军，朱婷婷，王南南，等. 腰痛宁胶囊组方不同有效部位细胞药理活性评价[J]. 世界科学技术-中医药现代化, 2015, 17(5):963-970. |
| [4] | 滕皓，周荣祥，张钢，等. COX-2与mPGES-1在肾透明细胞癌中的表达及临床意义[J]. 现代生物医学进展, 2012, 12(16):3141-3144. |
| [5] | 王静媛，陈阿梅，刘秀兰，等. 肺癌组织中cPLA2和mPGES-1的表达及意义[J]. 南昌大学学报(医学版)，2014, 54(4):9-14. |
| [6] | 屠洪斌，董志毅，王少墨，等. 原发性肺癌中医证型规律与化疗及靶向治疗的相关性研究[J]. 世界科学技术-中医药现代化，2014, 16(9):1997-2001. |
| [7] | 杨莉，阮文静，陈恩国，等. 血清NKX2-1蛋白在原发性肺癌患者中的诊断价值[J]. 浙江大学学报(医学版), 2012, 41(5):535-539. |
| [8] | 张畅斌，李沧海，隋峰，等. 桂枝汤苯丙烯类化合物对环氧合酶-2及前列腺素抑制的作用[J]. 中国实验方剂学杂志, 2012, 18(9):157-161. |
| [9] | 孙晓艳，王亚帝，何东宁，等. BAG-1S和COX-2基因在非小细胞肺癌中的表达及其对预后的意义[J]. 中国全科医学, 2014, 17(32):3840-3845. |
| [10] | 李韶今，张相民，李荣，等. 非小细胞肺癌组织中P-ACC及COX-2的相关性研究[J]. 中国肿瘤临床, 2014, 41(1):68-72. |
| [11] | 张双越，杜一飞，宋砚斌，等.前列腺素E<sub>2</sub>合成通路在口腔鳞状细胞癌发生过程中的表达和意义[J]. 口腔生物医学，2010, 1(4):186-189. |
| [12] | JIN J, LIN G, HUANG H, et al. Capsaicin mediates cell cycle arrest and apoptosis in human colon cancer cells via stabilizing and activating p53[J]. Int J Biol Sci, 2014, 10(3):285-295. |
| [13] | PRAMANIK KC, BOREDDY SR, SRIVASTAVA SK. Role of mitochondrial electron transport chain complexes in capsaicin mediated oxidative stress leading to apoptosis in pancreatic cancer cells[J]. PLoS One, 2011, 6(5):e20151. |
| [14] | CHAKRABORTY S, ADHIKARY A, MAZUMDAR M, et al. Capsaicin-induced activation of p53-SMAR1 auto-regulatory loop down-regulates VEGF in non-small cell lung cancer to restrain angiogenesis[J]. PLoS One, 2014, 9(6):e99743. |
| [15] | 苟云久，何晓东，谢定雄，等. 非小细胞肺癌组织中CD133表达及临床意义的Meta分析[J]. 中国组织工程研究，2013, 17(23):4292-4298. |
| [16] | 陈万灵，欧阳学农，余宗阳，等. 中晚期非小细胞肺癌常见中医证型与血清前炎症因子水平相关性研究[J]. 中华中医药杂志(原中国医药学报), 2012, 27(6):1718-1720. |
| [17] | 俞富祥，朱千东，余正平，等. 辣椒素抑制大鼠肝纤维化的实验研究[J]. 中国病理生理杂志, 2014, 30(1):91-95. |
| [18] | 何磊，孟翔凌，涂从银，等. PGE<sub>2</sub>在结直肠癌患者肿瘤组织和外周血中的临床意义[J]. 世界华人消化杂志, 2011, 19(2):205-208. |
| [19] | SUZUKI-YAMAMOTO T, TANAKA S, TSUKAYAMA I, et al. Dioscorea japonica extract down-regulates prostaglandin E2 synthetic pathway and induces apoptosis in lung cancer cells[J]. J Clin Biochem Nutr, 2014, 55(3):162-167. |
| [20] | KATHLEEN C, BROWN, TED R, et al. Capsaicin displays anti-proliferative activity against human small cell lung cancer in cell culture and nude mice models via the E2F pathway[J]. PLoS One, 2010, 5(4):e10243. |
