Research Article

大戟(Euphorbiae Ebracteolatae)治疗显着降低E6和L1的表达,增加HPV18感染的人类包皮角质形成细胞中p53和Rb的表达

卷 19, 期 1, 2019

页: [20 - 31] 页: 12

弟呕挨: 10.2174/1566524019666190226102713

价格: $65

摘要

背景:据报道,大戟(Euphorbiae Ebracteolatae)(REE)在治疗多发跖疣方面明显优于维生素A酸软膏。然而,REE对HPV18的影响仍不清楚。因此,目前的研究旨在研究REE对HPV18增殖的影响,并探讨其可能的分子机制。 方法:HFK和HFK-HPV18分别用水提取的单一或化合物REE,乙醇提取的单一或化合物REE,TNF-α和IFN处理3天。此外,含有HFK-HPV18和HFK的器官型筏分别用REE,IFN和TNF-α处理7天。用Brdu测量细胞增殖率。通过qPCR检测E6,L1,p53和Rb的mRNA表达。通过Western印迹检测p53,Rb和L1的蛋白质表达。 结果:与HFK组相比,HFK-HPV18组E6和L1的表达明显增高。与对照组相比,用REE,TNF-α和IFN处理的HFK-HPV18显示出显着较低的增殖率。在HFK-HPV18或含有HFK-HPV18的器官型筏中处理REE后,E6的mRNA表达显着降低,p53和Rb的mRNA表达显着增加。用REE处理显着增加p53和Rb的蛋白质表达,并降低HFK-HPV18或含有HFK-HPV18的器官型筏中L1的蛋白质表达。在所有REE配方中,乙醇提取物REE组中HFK-HPV18对增殖率和E6,L1表达的抑制以及p53和Rb表达的增加最高。 结论:REE处理的HFK-HPV18的增殖率显着降低。在HFK-HPV18或含有HFK-HPV18的器官型筏中REE处理后,E6和L1的表达显着降低,并且p53和Rb的表达显着更高。在所有REE配方中,乙醇提取的化合物REE对HPV18具有最高的保护作用。背景:据报道,大戟(Euphorbiae Ebracteolatae)(REE)在治疗多发跖疣方面明显优于维生素A酸软膏。然而,REE对HPV18的影响仍不清楚。因此,目前的研究旨在研究REE对HPV18增殖的影响,并探讨其可能的分子机制。

关键词: Radix Euphorbiae Ebracteolatae,HPV18,癌症,尖锐湿疣,角质形成细胞,HFK。Radix Euphorbiae Ebracteolatae

[1]
Ljubojevic S, Skerlev M. HPV-associated diseases. Clin Dermatol 2014; 32: 227-34.
[2]
Sawaya GF, Kulasingam S, Denberg TD, Qaseem A. Cervical Cancer Screening in Average-Risk Women: Best Practice Advice From the Clinical Guidelines Committee of the American College of Physicians. Ann Intern Med 2015; 162: 851-9.
[3]
Zhao K, Xu G, Jin R, Xu L. [Taxonomic studies on original plants of radix Euphorbiae ebracteolatae]. Zhongguo Zhongyao Zazhi 1995; 20: 5-6, 61.
[4]
He X, Xu P, He XF, et al. Efficacy of topical administration of Radix Euphorbiae Ebracteolatae on multiple plantar warts: A parallel randomized trial. Chin J Integr Med 2017.
[http://dx.doi.org/10.1007/s11655-017-2794-0]
[5]
Hoppe-Seyler K, Bossler F, Braun JA, Herrmann AL, Hoppe-Seyler F. The HPV E6/E7 Oncogenes: Key Factors for Viral Carcinogenesis and Therapeutic Targets. Trends Microbiol 2017; 26: 158-68.
[6]
Ershov VA, Il’inskaia EV. [Capsid protein L1 HPV-16 in a modified cervical epithelium]. Vopr Onkol 2013; 59: 47-51.
[7]
Buck CB, Day PM, Trus BL. The papillomavirus major capsid protein L1. Virology 2013; 445: 169-74.
[8]
Duerksen-Hughes PJ, Yang J, Schwartz SB. HPV 16 E6 blocks TNF-mediated apoptosis in mouse fibroblast LM cells. Virology 1999; 264: 55-65.
[9]
Thyrell L, Sangfelt O, Zhivotovsky B, et al. The HPV-16 E7 oncogene sensitizes malignant cells to IFN-alpha-induced apoptosis. J Interferon Cytokine Res 2005; 25: 63-72.
[10]
Satsuka A, Yoshida S, Kajitani N, Nakamura H, Sakai H. Novel human papillomavirus type 18 replicon and its application in screening the antiviral effects of cytokines. Cancer Sci 2010; 101: 536-42.
[11]
Wang S, Long S, Xiao S, Wu W, Hann SS. Decoction of Chinese Herbal Medicine Fuzheng Kang-Ai Induces Lung Cancer Cell Apoptosis via STAT3/Bcl-2/Caspase-3 Pathway. Evid Based Complement Alternat Med 2018; 2018: 8567905.
[12]
Gong X, Zhang Y, Pan J, Qu H. Optimization of the ethanol recycling reflux extraction process for saponins using a design space approach. PLoS One 2014; 9: e114300.
[13]
Motobu M, El-Abasy M, Na KJ, Hirota Y. Detection of mitogen-induced lymphocyte proliferation by bromodeoxyuridine (BrdU) incorporation in the chicken. J Vet Med Sci 2002; 64: 377-9.
[14]
Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)). Method Methods 2001; 25: 402-8.
[15]
Jeong DE, Lee Y, Lee SV. Western Blot Analysis of C. elegans Proteins. Methods Mol Biol 2018; 1742: 213-25.
[16]
Wilson R, Laimins LA. Differentiation of HPV-containing cells using organotypic “raft” culture or methylcellulose. Methods Mol Med 2005; 119: 157-69.
[17]
Bruno MT, Ferrara M, Fava V, Rapisarda A, Coco A. HPV genotype determination and E6/E7 mRNA detection for management of HPV positive women. Virol J 2018; 15: 52.
[18]
Ram BM, Dolpady J, Kulkarni R, et al. Human papillomavirus (HPV) oncoprotein E6 facilitates Calcineurin-Nuclear factor for activated T cells 2 (NFAT2) signaling to promote cellular proliferation in cervical cell carcinoma. Exp Cell Res 2017; 362: 132-41.
[19]
Thatte J, Massimi P, Thomas M, Boon SS, Banks L. The HPV E6 PDZ Binding Motif links DNA Damage Response Signaling to E6 Inhibition of p53 Transcriptional Activity. J Virol 2018; 92(16): e00465-18.
[20]
Kojima Y, Otsuki N, Kubo M, et al. Adenovirus-mediated transfer of HPV 16 E6/E7 antisense RNA combined with cisplatin inhibits cellular growth and induces apoptosis in HPV-positive head and neck cancer cells. Cancer Gene Ther 2018; 25(9-10): 274-83.
[21]
Norman I, Hjerpe A, Andersson S. High-risk HPV L1 capsid protein as a marker of cervical intraepithelial neoplasia in high-risk HPV-positive women with minor cytological abnormalities. Oncol Rep 2013; 30: 695-700.
[22]
Xu HM, Sun WY, Zhang G, Ni XH. [Detection and significance of HPV L1 capsid protein in cervical squamous intraepithelial lesions]. Zhonghua Bing Li Xue Za Zhi 2011; 40: 549-50.
[23]
Lee HJ, Yoon JK, Heo Y, et al. Therapeutic potential of an AcHERV-HPV L1 DNA vaccine. J Microbiol 2015; 53: 415-20.
[24]
Munagala R, Kausar H, Munjal C, Gupta RC. Withaferin A induces p53-dependent apoptosis by repression of HPV oncogenes and upregulation of tumor suppressor proteins in human cervical cancer cells. Carcinogenesis 2011; 32: 1697-705.
[25]
Guo KY, Han L, Li X, et al. Novel proteasome inhibitor delanzomib sensitizes cervical cancer cells to doxorubicin-induced apoptosis via stabilizing tumor suppressor proteins in the p53 pathway. Oncotarget 2018; 8: 114123-35.
[26]
Yang X, Lu L. Expression of HPV-16 E6 protein and p53 inactivation increases the uterine cervical cancer invasion. Drug Res (Stuttg) 2014; 65: 70-3.
[27]
Das S, Somasundaram K. Therapeutic potential of an adenovirus expressing p73 beta, a p53 homologue, against human papilloma virus positive cervical cancer in vitro and in vivo. Cancer Biol Ther 2006; 5: 210-7.
[28]
Sharma G, Rana NK, Singh P, Dubey P, Pandey DS, Koch B. p53 dependent apoptosis and cell cycle delay induced by heteroleptic complexes in human cervical cancer cells. Biomed Pharmacother 2017; 88: 218-31.
[29]
Sima N, Wang W, Kong D, et al. RNA interference against HPV16 E7 oncogene leads to viral E6 and E7 suppression in cervical cancer cells and apoptosis via upregulation of Rb and p53. Apoptosis 2008; 13: 273-81.
[30]
Deshpande R, Mansara P, Kaul-Ghanekar R. Alpha-linolenic acid regulates Cox2/VEGF/MAP kinase pathway and decreases the expression of HPV oncoproteins E6/E7 through restoration of p53 and Rb expression in human cervical cancer cell lines. Tumour Biol 2015; 37: 3295-305.
[31]
Zingue S, Nde CBM, Michel T, et al. Ethanol-extracted Cameroonian propolis exerts estrogenic effects and alleviates hot flushes in ovariectomized Wistar rats. BMC Complement Altern Med 2017; 17: 65.
[32]
Xie XL, Gi M, Fujioka M, et al. Ethanol-extracted propolis enhances BBN-initiated urinary bladder carcinogenesis via non-mutagenic mechanisms in rats. Food Chem Toxicol 2015; 83: 193-200.
[33]
Doi K, Fujioka M, Sokuza Y, et al. Chemopreventive Action by Ethanol-extracted Brazilian Green Propolis on Post-initiation Phase of Inflammation-associated Rat Colon Tumorigenesis. In Vivo 2017; 31: 187-97.

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy