芳姜黄酮对SiHa细胞增殖、迁移及侵袭的影响

doi:10.6040/j.issn.1671-7554.0.2018.1443

摘要/Abstract

摘要： 目的研究芳姜黄酮对子宫颈癌SiHa细胞体外增殖、迁移与侵袭的作用,并初步探讨其机制。方法体外培养SiHa细胞,不同浓度芳姜黄酮(0、20、40、80 mg/L)作用于细胞后,采用CCK8法检测SiHa细胞体外增殖情况;吉姆萨染色显微镜观察SiHa细胞凋亡情况;细胞划痕实验和Transwell小室检测SiHa细胞体外迁移和侵袭能力;流式细胞术分析确定SiHa细胞的诱导凋亡率;Western blotting检测SiHa细胞MMP2、MMP9及p53蛋白表达。结果芳姜黄酮可抑制SiHa细胞的体外增殖(F浓度=162.419,P<0.001;F时间=99.442,P<0.001;F浓度×时间=2.111,P=0.095)、迁移(F浓度=432.158,P<0.001;F时间=528.845,P<0.001)和侵袭(F浓度=434.362,P<0.001),且与其浓度、作用时间呈正相关;流式细胞仪分析表明,芳姜黄酮可诱导SiHa细胞凋亡(F浓度=482.690,P<0.001),且与其浓度呈正相关;Western blotting检测结果表明,经芳姜黄酮处理后,凋亡相关蛋白p53的表达明显上调(F浓度=2.086,P=0.045)、侵袭和转移相关蛋白MMP2、MMP9的表达下调(F浓度=18.906,P=0.001;F浓度=9.847,P=0.005)。结论芳姜黄酮具有抑制SiHa细胞体外增殖及诱导细胞凋亡的能力,其机制可能与调节凋亡相关蛋白p53表达有关;芳姜黄酮可能通过调节侵袭和转移相关蛋白MMP2、MMP9的表达,进而抑制SiHa细胞迁移与侵袭。

关键词: 芳姜黄酮, SiHa细胞, 凋亡, 迁移, 侵袭

Abstract: Objective To investigate the effect of ar-turmerone on the proliferation, migration and invasion of cervical cancer SiHa cells in vitro, and to preliminarily explore its mechanism. Methods SiHa cells were incubated with different concentrations of ar-turmerone(0, 20, 40, 80 mg/L), and cell proliferation was measured by CCK8. The apoptosis was observed by giemsa staining. The effects of ar-turmerone on migration and invasion capacity of SiHa cells were detected by cell scratch assay and transwell. The apoptosis was analyzed by flow cytometry. The expressions of MMP2, MMP9 and p53 protein in SiHa cells were detected by Western blotting. Results Ar-turmerone dose-dependently inhibited SiHa cells proliferation(F_{concentration}=162.419, P<0.001; F_time=99.442, P<0.001; F_{concentration×time}=2.111, P=0.095), migration(F_{concentration}=432.158, P<0.001; F_time=528.845, P<0.001)and invasion(F_{concentration}=434.362, P<0.001). 山东大学学报 (医学版)57卷6期 -罗梦颖,等.芳姜黄酮对SiHa细胞增殖、迁移及侵袭的影响 \=-Flow cytometry analysis showed that ar-turmerone could induce the apoptosis of SiHa cells in a dose-dependent manner(F_{concentration}=482.690, P<0.001). Western blotting results showed that ar-turmerone treatment significantly up-regulated the expression of apoptosis-related proteins p53(F_{concentration}=2.086, P=0.045)and down-regulated the expressions of invasion and metastasis related proteins MMP2 and MMP9(F_{concentration}=18.906, P=0.001; F_{concentration}=9.847, P=0.005). Conclusion Ar-turmerone has the ability to inhibit the proliferation and induce apoptosis of SiHa cells in vitro, and the mechanism is related to the regulation of apoptosis related protein p53 expression. In addition, ar-turmerone can inhibit the migration and invasion of SiHa cells, possibly through the regulation of the expressions of MMP2 and MMP9 protein.

Key words: Ar-turmerone, SiHa cell, Apoptosis, Migration, Invasion

中图分类号:

R285.5

罗梦颖,吴蓓,王叶,骆衡,曹煜. 芳姜黄酮对SiHa细胞增殖、迁移及侵袭的影响[J]. 山东大学学报 (医学版), 2019, 57(6): 68-74.

LUO Mengying, WU Bei, WANG Ye, LUO Heng, CAO Yu. Effect of ar-turmerone on poliferation, migration and invasion of cervical squamous cancer cell line SiHa[J]. Journal of Shandong University (Health Sciences), 2019, 57(6): 68-74.

参考文献

[1] Peralta-Zaragoza O, Deas J, Meneses-Acosta A, et al. Relevance of miR-21 in regulation of tumor suppressor gene PTEN in human cervical cancer cells[J]. BMC Cancer, 2016, 16: 215. doi:10.1186/s12885-016-2231-3.
[2] Zheng W, Liu Z, Zhang W, et al. miR-31 functions as an oncogene in cervical cancer[J]. Arch Gynecol Obstet, 2015, 292(5): 1083-1089.
[3] Chen Y, Wang H, Lin W, et al. ADAR1 overexpression is associated with cervical cancer progression and angiogenesis[J]. Diagn Pathol, 2017, 12(1): 12. doi:10.1186/s13000-017-0600-0.
[4] Barra F, Lorusso D, Leone Roberti Maggiore U, et al. Investigational drugs for the treatment of cervical cancer[J]. Expert Opin Investig Drugs, 2017, 26(4): 389-402.
[5] Brucker SY, Ulrich UA. Surgical treatment of early-stage cervical cancer[J]. Oncol Res Treat, 2016, 39(9): 508-514.
[6] Liu C, Liao JZ, Li PY. Traditional Chinese herbal extracts inducing autophagy as a novel approach in therapy of nonalcoholic fatty liver disease[J]. World J Gastroenterol, 2017, 23(11): 1964-1973.
[7] Reis FS, Lima RT, Morales P, et al. Methanolic extract of Ganoderma lucidum induces autophagy of AGS human gastric tumor cells[J]. Molecules, 2015, 20(10): 17872-17882.
[8] Yu N, Xiong Y, Wang C. Bu-Zhong-Yi-Qi decoction, the water extract of Chinese traditional herbal medicine, enhances cisplatin cytotoxicity in A549/DDP cells through induction of apoptosis and autophagy[J]. Biomed Res Int, 2017, 2017: e3692797. doi:10.1155/2017/3692797.
[9] Newman DJ, Cragg GM. Natural products as sources of new drugs from 1981 to 2014[J]. J Nat Prod, 2016, 79(3): 629-661.
[10] 庞邦斌, 银胜高, 黄云兰, 等. 不同产地姜黄药材的质量研究[J]. 华西药学杂志, 2014, 29(3): 308-310. PANG Bangbin, YIN Shenggao, HUANG Yunlan, et al. Quality assessment on Curcuma longa from the different producing areas[J]. West China Journal of Pharmaceutical Sciences, 2014, 29(3): 308-310.
[11] Gounder DK, Lingamallu J. Comparison of chemical composition and antioxidant potential of volatile oil from fresh, dried and cured turmeric(Curcuma longa)rhizomes[J]. Industrial Crops and Products, 2012, 38: 124-131. doi:10.1016/j.indcrop.2012.01.014.
[12] Prakash P, Misra A, Surin WR, et al. Anti-platelet effects of Curcuma oil in experimental models of myocardial ischemia-reperfusion and thrombosis[J]. Thromb Res, 2011, 127(2): 111-118.
[13] Kim D, Suh Y, Lee H, et al. Immune activation and antitumor response of ar-turmerone on P388D1 lymphoblast cell implanted tumors[J]. Int J Mol Med, 2013, 31(2): 386-392.
[14] Tundis R, Xiao J, Loizzo MR. Annona species(Annonaceae): a rich source of potential antitumor agents?[J]. Ann N Y Acad Sci, 2017, 1398(1): 30-36.
[15] Zhang X, Wang R, Chen G, et al. The effects of curcumin-based compounds on proliferation and cell death in cervical cancer cells[J]. Anticancer Res, 2015, 35(10): 5293-5298.
[16] Shang HS, Chang CH, Chou YR, et al. Curcumin causes DNA damage and affects associated protein expression in HeLa human cervical cancer cells[J]. Oncol Rep, 2016, 36(4): 2207-2215.
[17] Joshi JV, Jagtap SS, Paradkar PH, et al. Cytologic follow up of Low-grade Squamous Intraepithelial Lesions in Pap smears after integrated treatment with antimicrobials followed by oral turmeric oil extract[J]. J Ayurveda Integr Med, 2016, 7(2): 109-112.
[18] Forbes-Hernández TY, Giampieri F, Gasparrini M, et al. The effects of bioactive compounds from plant foods on mitochondrial function: a focus on apoptotic mechanisms[J]. Food Chem Toxicol, 2014, 68: 154-182. doi:10.1016/j.fct.2014.03.017.
[19] Tuzlak S, Kaufmann T, Villunger A. Interrogating the relevance of mitochondrial apoptosis for vertebrate development and postnatal tissue homeostasis[J]. Genes Dev, 2016, 30(19): 2133-2151.
[20] Wu CC, Bratton SB. Regulation of the intrinsic apoptosis pathway by reactive oxygen species[J]. Antioxid Redox Signal, 2013, 19(6): 546-558.
[21] Thornborrow EC, Patel S, Mastropietro AE, et al. A conserved intronic response element mediates direct p53-dependent transcriptional activation of both the human and murine bax genes[J]. Oncogene, 2002, 21(7): 990-999.
[22] Wu Y, Mehew JW, Heckman CA, et al. Negative regulation of Bcl-2 expression by p53 in hematopoietic cells[J]. Oncogene, 2001, 20(2): 240-251.
[23] Chen YR, Tan TH. Lack of correlation in JNK activation and p53-dependent Fas expression induced by apoptotic stimuli[J]. Biochem Biophys Res Commun, 1999, 256(3): 595-599.
[24] Gough MJ, Killeen N, Weinberg AD. Targeting macrophages in the tumour environment to enhance the efficacy of αOX40 therapy[J]. Immunology, 2012, 136(4): 437-447.
[25] Chen K, Zhang S, Ji Y, et al. Baicalein inhibits the invasion and metastatic capabilities of hepatocellular carcinoma cells via down-regulation of the ERK pathway[J]. PLoS One, 2013, 8(9): e72927. doi:10.1371/journal.pone.0072927.
[26] Shuman Moss LA, Jensen-Taubman S, Stetler-Stevenson WG. Matrix metalloproteinases: changing roles in tumor progression and metastasis[J]. Am J Pathol, 2012, 181(6): 1895-1899.
[27] Littlepage LE, Sternlicht MD, Rougier N, et al. Matrix metalloproteinases contribute distinct roles in neuroendocrine prostate carcinogenesis, metastasis, and angiogenesis progression[J]. Cancer Res, 2010, 70(6): 2224-2234.

相关文章 15

[1]	张士宝刘庆勇阮喜云陈杰张建军李宗武杨广笑王全颖. NT₄-SAC-HA₂-TAT融合基因表达载体的构建及鉴定[J]. 山东大学学报(医学版), 2209, 47(6): 15-19.
[2]	鹿向东杨伟徐广明曲元明. 脑膜瘤中PPAR-γ的表达及曲格列酮对脑膜瘤培养细胞生长的影响[J]. 山东大学学报(医学版), 2209, 47(6): 65-.
[3]	陈杨,冯莹,卢晓,郑蓉. 半乳糖凝集素-3通过PI3K/Akt/mTOR通路促进巨噬细胞自噬分化[J]. 山东大学学报 (医学版), 2026, 64(4): 14-22.
[4]	殷悦,莫振飞,吴培昕,刘金霞,魏元辉,任佳博,李春笋. GPX1基因在肺癌中的表达特征及其对肺腺癌细胞增殖、迁移、侵袭、凋亡的影响[J]. 山东大学学报 (医学版), 2026, 64(1): 65-73.
[5]	韩觉明,王晖,吴倩,郑慧玲,朱琳. B4GALNT4促进肺腺癌细胞增殖、迁移和侵袭能力[J]. 山东大学学报 (医学版), 2025, 63(7): 23-31.
[6]	李响,张艺,王雪纯,徐梦超,王月兰. 氧化应激在创伤性脑损伤诱发急性肺损伤中的研究进展[J]. 山东大学学报 (医学版), 2025, 63(2): 118-124.
[7]	李观强,施昱诚,朱可涵,胡波,黄献琛,孙元,李笃信,张喜成. 蜗牛粘液来源的活性肽SK-14促进成纤维细胞的增殖和迁移[J]. 山东大学学报 (医学版), 2025, 63(11): 1-7.
[8]	刘振昆,吕纪玲,徐伟伟,马力天,张才擎. BALF tNGS检测及培养对NSCLC合并IPFD的诊断价值[J]. 山东大学学报 (医学版), 2025, 63(11): 36-45.
[9]	张洁,张芳芳,王靖楠,李泽宇,宋颖,李娜. circ_0000144在乳腺癌中的表达及其对乳腺癌细胞增殖、迁移和侵袭能力的影响[J]. 山东大学学报 (医学版), 2025, 63(1): 35-42.
[10]	杜学识,倪向敏,梁馨予,白倩,朱文艺,王建. 雌马酚对DN的保护作用及潜在靶点[J]. 山东大学学报 (医学版), 2024, 62(8): 49-58.
[11]	王静,刘晓菲,曾荣,许长娟,张锦涛,董亮. 基于机器学习算法鉴定哮喘的坏死性凋亡相关生物标志物[J]. 山东大学学报 (医学版), 2024, 62(7): 21-32.
[12]	张学宇,张学海,孙文青,刘晗,姜金波,刘寒,李远,陈晓梅. 重症新型冠状病毒肺炎伴侵袭性肺曲霉病及反复致命性消化道出血1例[J]. 山东大学学报 (医学版), 2024, 62(7): 56-61.
[13]	姜子晗,芦兴晨,孙露,赵蕙琛,左丹,马小莉,刘元涛,张玉超. NR4A1通过IκBα/NF-κB通路调控过氧化氢诱导人脐静脉内皮细胞凋亡的机制[J]. 山东大学学报 (医学版), 2024, 62(3): 11-19.
[14]	曹华琳,贾彦召,曲莉,尹昕. CircFAT1调节miR-296-3p/MAPRE1轴对鼻咽癌细胞增殖、凋亡和放疗敏感性的影响[J]. 山东大学学报 (医学版), 2023, 61(9): 38-46.
[15]	高玉杰,龙启福,胡英,许玉珍,王茹,永胜. 生物信息学鉴定低氧诱导小鼠肾脏线粒体损伤的Hub基因及其作用机制[J]. 山东大学学报 (医学版), 2023, 61(9): 57-68.

多维度评价

Viewed

Full text

Abstract

Cited

Shared

Discussed