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中华肺部疾病杂志(电子版) ›› 2020, Vol. 13 ›› Issue (03) : 314 -318. doi: 10.3877/cma.j.issn.1674-6902.2020.03.005

论著

姜黄素对肺癌A549细胞迁移和侵袭的影响
谭丹1, 曾小琴2, 徐伟1, 陈戬3, 周人杰1,()   
  1. 1. 400037 重庆,陆军(第三)军医大学第二附属医院急诊与全科医学中心
    2. 400037 重庆,陆军(第三)军医大学第二附属医院呼吸与危重症医学科
    3. 400037 重庆,陆军(第三)军医大学第二附属医院全军免疫学研究所
  • 收稿日期:2020-03-11 出版日期:2020-06-25
  • 通信作者: 周人杰
  • 基金资助:
    国家自然科学基金资助项目(30972964)

Effect of curcumine on migration and invasion of A549 cells

Dan Tan1, Xiaoqin Zeng2, Wei Xu1, Jian Chen3, Renjie Zhou1,()   

  1. 1. Emergency and General Medical Center, Second Affiliated Hospital, Army Military Medical University, Chongqing 400037, China
    2. Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital, Army Military Medical University, Chongqing 400037, China
    3. Military Institute of Immunology, Second Affiliated Hospital, Army Military Medical University, Chongqing 400037, China
  • Received:2020-03-11 Published:2020-06-25
  • Corresponding author: Renjie Zhou
引用本文:

谭丹, 曾小琴, 徐伟, 陈戬, 周人杰. 姜黄素对肺癌A549细胞迁移和侵袭的影响[J/OL]. 中华肺部疾病杂志(电子版), 2020, 13(03): 314-318.

Dan Tan, Xiaoqin Zeng, Wei Xu, Jian Chen, Renjie Zhou. Effect of curcumine on migration and invasion of A549 cells[J/OL]. Chinese Journal of Lung Diseases(Electronic Edition), 2020, 13(03): 314-318.

目的

探讨姜黄素对肺癌A549细胞侵袭迁移力的影响及其机制。

方法

利用不同浓度姜黄素处理正常肺上皮细胞,台盼蓝法检测药物细胞毒性;不同浓度的姜黄素作用于A549细胞,MTT法测定A549细胞增殖水平;细胞划痕实验和Transwell实验分别测定药物处理后A549细胞的迁移和侵袭能力变化情况;Werstern blot测定A549细胞中于侵袭迁移有关的表皮生长因子受本(EGFR)、E-型钙黏蛋白(E-cadherin)、N-型钙黏蛋白(N-cadherin)蛋白的表达。

结果

姜黄素浓度在0~40 μg/ml时正常肺上皮病死率低,差异无明显统计学差异(P>0.05),表明姜黄素对正常肺上皮细胞的不良反应小;MTT实验结果显示姜黄素以浓度依赖的方式抑制A549细胞的增殖,各组与对照组相比均具有统计学意义(P<0.01);细胞划痕实验显示姜黄素以浓度依赖的方式抑制A549细胞的迁移能力,各组与对照组相比均具有统计学意义(P<0.01);Transwell实验显示姜黄素以浓度依赖的方式抑制A549细胞的侵袭能力,各组与对照组相比均具有统计学意义(P<0.01);Western blot显示姜黄素处理A549细胞后EGFR蛋白(P<0.01)和N-cadherin蛋白表达降低(P<0.01),E-cadherin蛋白表达升高(P<0.01)。

结论

一定浓度内姜黄素细胞毒性低,姜黄素能够抑制A549的增殖、迁移和侵袭,可能是通过调节EGFR、N-cadherin、E-cadherin蛋白从而逆转上皮间质转化过程。

Objective

To explore the effect and mechanism of curcumine on the migration and invasion of A549 cells.

Methods

Trypan blue dye exclusion assay was used to determine the effect of various concentrations of curcumine on the cell death rate. The proliferation of A549 cells was detected by MTT assay. The migration and invasion of A549 cells were determined by wound scratch assay and Transwell assay, respectively. The expression levels of EGFR, E-cadherin and N-cadherin in A549 cells affected by curcumine were detected by Western blotting method.

Results

When the curcumine concentration was 0-40 μg/ml, the mortality rate of the normal lung epithelial cells was low, and the difference was not statistically significant (P>0.05), indicating that curcumine had little toxic and side effects on the normal lung epithelial cells. The MTT results showed that curcumine inhibited the proliferation of A549 cells in a concentration-dependent manner, compared with the control group, and statistical significant difference was found between the two groups (P<0.01). The cell scratch experiment showed that the migration ability of A549 cells was reduced after treatment of curcumine for 24 hours, compared with the control group, and statistical significant difference was found between the two groups (P<0.01). Transwell assay showed that the invasiveness of A549 cells was decreased with the least amount of curcumine, compared with the control group, and statistical significant difference was found between the two groups (P<0.01). Western blotting showed that the expression of epidermal growth factor receptor (EGFR, P<0.01) and N-cadherin protein were decreased (P<0.01) and the expression of E-cadherin protein was increased (P<0.01) after treatment of 40 μg/ml of curcumine on A549 cells, compared with the control group, and statistical significant difference was found between the two groups.

Conclusion

Curcumine can inhibit the proliferation, migration and invasion of A549 cells probably through down-regulating the expression of EGFR and N-cadherin and regulating the expression of E-cadherin, and therefore reversing the process of epithelial stromal transformation.

图1 姜黄素对人正常肺上皮细胞病死率的影响;注:*P<0.01,与对照组比较
图2 姜黄素对A549细胞增殖的影响;注:*P<0.05,#P<0.01,与对照组比较
表1 姜黄素对A549细胞增殖的影响(±sn=5,48 h)
图3 A549细胞划痕实验光镜照片(HE×100);注:*P<0.01,与对照组比较;#P<0.01,与较低剂量组比较
图4 A549细胞Transwell侵袭实验光镜照片(HE×100);注:*P<0.01,与对照组比较;#P<0.01,与较10 μg剂量组比较
图5 Western blot显示各组中EGFR、E-cadherin以及N-cadher蛋白的表达变化(±sn=3);注:*P<0.01 vs. 1; #P<0.01 vs 2; ∧P<0.01 vs. 3
1
钱桂生. 肺癌不同病理类型发病率的变化情况及其原因[J/CD]. 中华肺部疾病杂志(电子版), 2011, 4(1): 1-5.
2
陈艳丽,王媛媛,张 勇,等. 中晚期非小细胞肺癌患者化疗前后T淋巴细胞亚群表达差异分析及临床意义[J/CD]. 中华肺部疾病杂志(电子版), 2020, 13(1): 13-17.
3
李帅帅,孙 军. 姜黄素对人肝癌细胞BE-7402中环氧合酶-2表达影响的研究[J]. 中国医科大学学报,2014, 43(3): 222-225.
4
张 英,李冬梅,邢 颖. 姜黄素的药理作用与载体研究进展[J]. 中国药房,2015, 26(13): 1850-1853.
5
Liu S, Wang Z, Xu B, et al. Intermittent hypoxia reduces microglia proliferation and induces DNA damage in vitro[J]. Iran J Basic Med Sci, 2016, 19(5): 497-502.
6
Juergens RA, Brahmer JR. Adjuvant treatment in non-small cell lung cancer: Where are we now?[J]. J Natl Compr Canc Netw, 2006, 4(6): 595-600.
7
李 牧,王 丽,刘海莉,等. 姜黄素通过降低一氧化氮合酶水平抑制宫颈癌HeLa细胞的侵袭和转移[J]. 南方医科大学学报,2013, 33(12): 1752-1756.
8
Tateishi M, Ishida T, Mitsudomi T, et al. Immunohistochemical evidence of autocrine growth factors in adenocarcinoma of the human lung[J]. Cancer Res, 1990, 50(21): 7077-7080.
9
Barker AJ, Gibson KH, Grdundy, et al. Studies leading to the identification of ZD1839?(IRESSA): an orally active, selective epidermal growth factor receptor tyrosine kinase inhibitor targeted to the treatment of cancer[J]. Bioorg Med Chem Lett, 2001, 11(14): 1911-1914.
10
朱丛中,刘 娟,王新允,等. 应用组织芯片法检测EGFR、COXZ在肺癌中的表达及生物学意义[J]. 中国肺癌杂志,2010, 13(2): 107-111.
11
Christiansen JJ, Rajasekaran AK. Reassessing epithelial to mesenchymal transition as a prerequisite for carcinoma invasion and metastasis[J]. Cancer Res, 2006, 66(17): 8319-8326.
12
Galera-Ruiz, Rios MJ, Gonzalez-Campora, et al. The cadherin-catenin complex in nasopharyngeal carcinoma[J]. Eur Arch Otorhinolaryngol, 2011, 268(9): 1335-1341.
13
Maseki S, Ijichi K, Tanaka H, et al. Acquisition of EMT phenotype in the gefitinib-resistant cells of a head and neck squamous cell carcinoma cell line through Akt/GSK-3β/snail signalling pathway[J]. Br J Cancer, 2012, 106(6): 1194-1204.
14
Rosano L, Cianfrocca R, Spinella F, et al. Acquisition of chemoresistance and EMT phenotype is linked with activation of the endothelin A receptor pathway in ovarian carcinoma cells[J]. Clin Cancer Res, 2011, 17(8): 2350-2360.
15
Foroni C, Broggini M, Generali D, et al. Epithelial-mesenchymal transition and breast cancer: Role, molecular mechanism and clinical impact[J]. Cancer Treat Rev, 2012, 38(6): 689-697.
16
Fu Q, Liu X, Liu Y, et al. MicroRNA-335 and-543 suppress bone metastasis in prostate cancer via targeting endothelial nitric oxide synthase[J]. Int J Mol Med, 2015, 36(5): 1417-1425.
17
Liu S, Wang Z, Xu B, et al. Intermittent hypoxia reduces microglia proliferation and induces DNA damage in vitro[J]. Iran J Basic Med Sci, 2016, 19(5): 497-502.
18
Ranjan AP, Mukerjee A, Gdowski A, et al. Curcumin-ER prolonged subcutaneous delivery for the treatment of non-small cell lung cancer[J]. JBiomed Nanotechnol, 2016, 12(4): 679-688.
19
周晶晶,郑昱辰,李明月,等. 姜黄素的药理作用研究进展[J]. 吉林医药学院学报,2016, 37(4): 304-307.
20
戴 莉,杨 炯,潘雪凯,等. 姜黄素对肺腺癌A549细胞裸鼠移植瘤的抑制作用及其机制[J]. 中华实验外科杂志,2016, 33(10): 2358-2361.
21
Chong CR, Jänne PA. The quest to overcome resistance to EGFR-targeted therapies in cancer[J]. Nature Medicine, 2013, 19(11): 1389.
22
李松霖,谭群友,王如文,等. 新型姜黄素纳米粒对Lewis肺癌细胞增殖、凋亡的影响[J]. 第三军医大学学报,2015, 37(2): 141-145.
23
赵 莹,李英姿. 姜黄素对非小细胞肺癌A459细胞增殖及CDH13甲基化状态的影响[J]. 山东医药,2017, 57(6): 9-12.
24
Siddappa G, Kulsum S, Ravindra DR, et al. Curcumin and metformin mediated chemoprevention of oral cancer is associated with inhibition of cancer stem cells[J]. Mol Carcinog, 2017, 56(11): 2446.
25
Li ZC, Zhang LM, Wang HB, et al. Curcumin inhibits lung cancer pro-gression and metastasis through induction of FOXO1[J]. Tumor Biology, 2014, 35(1): 111.
26
Lu Y, Wei C, Xi Z. Curcumin suppresses proliferation and invasion in non-small cell lung cancer by modulation of MTA1-mediated Wnt/β-catenin pathway[J]. In Vitro Cellular & Developmental Biology-Animal, 2014, 50(9): 840.
27
Jin H, Qiao F, Wang Y, et al. Curcumin inhibits cell proliferation and induces apoptosis of human non-small cell lung cancer cells through the upregulation of miR-192-5p and suppression of PI3K/Akt signaling pathway[J]. Oncol Reports, 2015, 34(5): 2782.
28
Wang A, Wang J, Zhang S, et al. Curcumin inhibits the development of non-small cell lung cancer by inhibiting autophagy and apoptosis[J]. Exp Ther Med, 2017, 14(5): 5075.
29
张卫平,王 珏,冉 冉. 姜黄素逆转非小细胞肺癌TKI靶向药物耐药机制的研究[J]. 中国现代医生,2017, 55(25): 37-41.
30
Shishodia S, Chaturvedi MM, Aggarwal BB. Role of Curcumin in Cancer Therapy[J]. Curr Probl Cancer, 2007, 31(4): 243-305.
31
Liu S, Wang Z, Xu B, et al. Intermittent hypoxia reduces microglia proliferation and induces DNA damage in vitro[J]. Iran J Basic Med Sci, 2016, 19(5): 497-502.
32
Rivera M, Ramos Y, Rodríguez-Valentín M, et al. Targeting multiple pro-apoptotic signaling pathways with curcumin in prostate cancer cells[J]. PLoS One, 2017, 12(6): e0179587.
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