您的位置:山东大学 -> 科技期刊社 -> 《山东大学学报(医学版)》

山东大学学报 (医学版) ›› 2019, Vol. 57 ›› Issue (6): 68-74.doi: 10.6040/j.issn.1671-7554.0.2018.1443

• • 上一篇    

芳姜黄酮对SiHa细胞增殖、迁移及侵袭的影响

罗梦颖1,吴蓓2,王叶1,骆衡3,4,曹煜1   

  1. 1. 贵州医科大学, 贵州 贵阳 550004;2. 解放军第44医院妇产科, 贵州 贵阳 550009;3. 药用植物功效与利用国家重点实验室, 贵州 贵阳550014;4. 贵州省中国科学院天然产物化学重点实验室, 贵州 贵阳 550014
  • 发布日期:2022-09-27
  • 通讯作者: 曹煜. E-mail:2692327139@qq.com
  • 基金资助:
    贵州省中药现代化专项项目(2012-5018);贵阳市科技计划项目(20161001)

Effect of ar-turmerone on poliferation, migration and invasion of cervical squamous cancer cell line SiHa

LUO Mengying1, WU Bei2, WANG Ye1, LUO Heng3,4, CAO Yu1   

  1. 1. Guizhou Medical University, Guiyang 550004, Guizhou, China;
    2. Department of Gynecology and Obstetrics, the 44 Hospital of Peoples Liberation Army, Guiyang 550009, Guizhou, China;
    3. State Key Laboratory of Functions and Applications of Medicinal Plants, Guiyang 550014, Guizhou, China;
    4. Key Laboratory of Chemistry for Natural Products of Guizhou Province, Chinese Academy of Sciences, Guiyang 550014, Guizhou, China
  • Published:2022-09-27

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(Fconcentration=162.419, P<0.001; Ftime=99.442, P<0.001; Fconcentration×time=2.111, P=0.095), migration(Fconcentration=432.158, P<0.001; Ftime=528.845, P<0.001)and invasion(Fconcentration=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(Fconcentration=482.690, P<0.001). Western blotting results showed that ar-turmerone treatment significantly up-regulated the expression of apoptosis-related proteins p53(Fconcentration=2.086, P=0.045)and down-regulated the expressions of invasion and metastasis related proteins MMP2 and MMP9(Fconcentration=18.906, P=0.001; Fconcentration=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
[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.
[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] 赵舸,邹存华,宋冬冬,赵淑萍. 丹参酮IIA对子宫内膜癌细胞增殖与凋亡的影响[J]. 山东大学学报 (医学版), 2022, 60(9): 53-58.
[4] 张振伟,李佳,陈克明. IGF2BP2/m6A/ITGA5信号轴调控肾透明细胞增殖和迁移[J]. 山东大学学报 (医学版), 2022, 60(9): 74-84.
[5] 孙丽娜,杜晓晓,张红娟,孟金来. 人类白细胞抗原G调控蜕膜自然杀伤细胞促进滋养细胞侵袭[J]. 山东大学学报 (医学版), 2022, 60(6): 41-45.
[6] 刘敏,张玉超,马小莉,刘昕宇,孙露,左丹,刘元涛. 孤核受体NR4A1在H2O2诱导小鼠肾脏足细胞损伤中的作用[J]. 山东大学学报 (医学版), 2022, 60(5): 16-21.
[7] 陈兆波,方敏,薛浩然,刘春艳. 去泛素化酶USP35促进非小细胞肺癌细胞迁移和侵袭[J]. 山东大学学报 (医学版), 2022, 60(4): 30-37.
[8] 钟黎黎,盛莹,郭江虹,阳双健,何宜静. LncRNA-UCA1通过靶向调控miR-182-5p对滋养细胞侵袭与转移的影响[J]. 山东大学学报 (医学版), 2022, 60(3): 76-82.
[9] 李卉,姜朝阳,刘岩,张曼. 组蛋白去乙酰化酶SIRT1调控氧化低密度脂蛋白诱导巨噬细胞凋亡的表达[J]. 山东大学学报 (医学版), 2022, 60(1): 6-12.
[10] 卢游,且迪,伍晋辉,杨凡. 干预Sonic Hedgehog信号通路对宫内发育迟缓新生大鼠学习记忆能力的影响[J]. 山东大学学报 (医学版), 2021, 59(5): 82-89.
[11] 南莉,杨凯转,张一帆. 室内照明白色发光二极管对大鼠视网膜的影响[J]. 山东大学学报 (医学版), 2021, 59(4): 56-62.
[12] 孔雪,李娟,段伟丽,史爽,李培龙,杜鲁涛,毛海婷,王传新. 长链非编码RNA AC012073.1对乳腺癌细胞迁移侵袭的影响及临床价值[J]. 山东大学学报 (医学版), 2021, 59(4): 70-78.
[13] 刘淑丹,张飞燕,郭松林,梁雪云,陈冬梅. 氧化苦参碱改善缺氧缺血引起的HaCaT细胞氧化应激损伤[J]. 山东大学学报 (医学版), 2021, 59(3): 26-34.
[14] 薛源,林雪艳,徐歌,田永杰. 低氧诱导因子-1α在子宫内膜异位症患者血清中的表达和对在位子宫内膜间质细胞上皮-间质转化的影响[J]. 山东大学学报 (医学版), 2021, 59(2): 41-47.
[15] 陈国丹,周勤,刘治玲,李福艳,朱庆章,于永梅,曾庆师. 6例盆腔侵袭性血管粘液瘤影像特征[J]. 山东大学学报 (医学版), 2021, 59(2): 55-59.
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed   
No Suggested Reading articles found!