山东大学学报 (医学版) ›› 2018, Vol. 56 ›› Issue (1): 70-75.doi: 10.6040/j.issn.1671-7554.0.2017.138
丁长宽,陈健行
DING Changkuan, Jason Chen
摘要: 目的 观察蛋白酶体抑制剂硼替佐米(BTZ)联合顺铂(CIS)对宫颈癌HeLa细胞增殖的影响并研究其相关机制。 方法 将Hela细胞分为NC组、CIS组、BTZ组、C&B组,分别以DMEM培养液、含CIS的培养液、含BTZ的培养液、含CIS及BTZ的培养液培养。以CCK-8法检测各组细胞的增殖抑制率,Western blotting法检测各组细胞中p53与Rb蛋白的表达水平,流式细胞仪检测细胞凋亡率。组间比较采用析因设计资料的方差分析。 结果 C&B组细胞增殖抑制率高于其他各组(P<0.05)。CIS组及C&B组中p53表达量较高(P<0.05),BTZ组与NC组相比差异无统计学意义。与NC组相比,BTZ组Rb表达量较高(P<0.05),CIS组、C&B组与NC组相比,差异无统计学意义。流式结果示CIS和BTZ在诱导细胞凋亡方面具有交互作用。 结论 CIS可能通过调控p53通路对宫颈癌HeLa细胞增殖产生抑制作用,而BTZ可能通过调控Rb通路对宫颈癌HeLa细胞增殖产生抑制作用,且BTZ与CIS联用在抑制HeLa细胞增殖方面具有协同交互作用。
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| [1] Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016[J]. CA Cancer J Clin, 2016, 66(1): 7-30. [2] Flagg EW, Schwartz R, Weinstock H. Prevalence of anogenital warts among participants in private health plans in the United States, 2003-2010: potential impact of human papillomavirus vaccination[J]. Am J Public Health, 2013, 103(8): 1428-1435. [3] Heley S. Human papillomavirus: beware the infection you cant see[J]. Aust Fam Physician, 2003, 32(5): 311-315. [4] de Villiers EM. Cross-roads in the classification of papillomaviruses[J]. Virology, 2013, 445(1-2): 2-10. [5] Jenkins D. A review of cross-protection against oncogenic HPV by an HPV-16/18 AS04-adjuvanted cervical cancer vaccine: importance of virological and clinical endpoints and implications for mass vaccination in cervical cancer prevention[J]. Gynecol Oncol, 2008, 110(Suppl 1): 18-25. [6] Nachajova M, Brany D, Dvorska D. Telomerase and the process of cervical carcinogenesis[J]. Tumor Biology, 2015, 36(10): 7335-7338. [7] Kennedy EM, Kornepati AV, Goldstein M, et al. Inactivation of the human papillomavirus E6 or E7 gene in cervical carcinoma cells by using a bacterial CRISPR/Cas RNA-guided endonuclease[J]. J Virol, 2014, 88(20):11965-11972. [8] Shiho O, Ning M, Raynoo T. DNA Damage in inflammation-related carcinogenesis and cancer stem cells[J]. Oxid Med Cell Longev, 2013, 2013: 387014. doi: 10.1155/2013/387014. [9] 蒲业迪, 李丽珍,马道新,等. 硼替佐米耐药多发性骨髓瘤细胞株KM3/BTZ的建立[J]. 山东大学学报(医学版), 2013, 51(2): 33-36. PU Yedi, LI Lizhen, MA Daoxin, et al. Establishment of a bortezomib-resistant cell line KM3 /BTZ of human multiple myeloma[J].Journal of Shandong University(Health Sciences), 2013, 51(2): 33-36. [10] 钟明星,邱帅. 硼替佐米联合地塞米松用于多发性骨髓瘤治疗的临床观察[J]. 中国医院药学杂志, 2016, 36: 292. [11] 任金海,郭晓楠. 多发性骨髓瘤诊断与治疗的研究进展[J]. 临床荟萃, 2017, 32(2): 177-180. REN Jinhai, GUO Xiaonan. Research progress of diagnosis and treatment of multiple myeloma[J]. Clinical Fous, 2017, 32(2): 177-180. [12] Tewari KS, Sill MW, Long HJ, et al. Improved survival with bevacizumab in advanced cervical cancer[J]. N Engl J Med, 2014, 370(8): 734-743. [13] Virag P, Perde-Schrepler M, Fischer-Fodor E, et al. Superior cytotoxicity and DNA cross-link induction by oxaliplatin versus cisplatin at lower cellular uptake in colorectal cancer cell lines[J]. Anticancer Drugs, 2012, 23(10): 1032-1038. [14] 刘亚飞,张奇舒,袁首道,等. HPV永生化细胞系与SiHa细胞系蛋白质表达差异的质谱分析[J]. 山东大学学报(医学版), 2015, 53(3): 22-26. LIU Yafei, ZHANG Qishu, YUAN Shoudao, et al. Mass spectrometry analysis of differentially expressed proteins between HPV immortalized cell line and SiHa cell line[J]. Journal of Shandong University(Health Sciences), 2015, 53(3): 22-26. [15] 孙晓莉, 高美华, 王在秋, 等. HPV-DNA与TCT联合检测在宫颈癌诊断中的应用[J]. 现代生物医学进展, 2012, 12(9):1745-1747. SUN Xiaoli, GAO Meihua, WANG Zaiqiu, et al. Application of HPV-DNA detecting with TCT test in cervical carcinoma diagnosis[J]. Progress in Modern Biomedicine, 2012, 12(9): 1745-1747. [16] Toft L, Storgaard M, Muller M, et al. Comparison of the immunogenicity and reactogenicity of Cervarix and Gardasil human papillomavirus vaccines in HIV-infected adults: a randomized, double-blind clinical trial[J]. J Infect Dis, 2014, 209(8): 1165-1173. [17] Ljubojevic S. The human papillomavirus vaccines[J]. Acta Dermatovenerol Croat, 2006, 14(3): 208. [18] Stillo M, Carrillo Santisteve P, Lopalco PL. Safety of human papillomavirus vaccines: a review[J]. Expert Opin Drug Saf, 2015, 14(5): 697-712. [19] Barac YD, Emrich F, Krutzwakd-Josefson E, et al. The ubiquitin-proteasome system: a potential therapeutic target for heart failure[J]. J Heart Lung Transplant, 2017, 36(7): 708-714. [20] Tomaic V, Pim D, Thomas M, et al. Regulation of the human papillomavirus type 18 E6/E6AP ubiquitin ligase complex by the HECT domain-containing protein EDD[J]. J Virol, 2011, 85(7): 3120-3127. [21] Todorovic B, Hung K, Massimi P, et al. Conserved region 3 of human papillomavirus 16 E7 contributes to deregulation of the retinoblastoma tumor suppressor[J]. J Virol, 2012, 86(24): 13313-13323. [22] Au Yeung CL, Tsang TY, Yau PL, et al. Human papillomavirus type 16 E6 induces cervical cancer cell migration through the p53/microRNA-23b/urokinase-type plasminogen activator pathway[J]. Oncogene, 2011, 30(21): 2401-2410. [23] Nevins JR. The Rb/E2F pathway and cancer[J]. Hum Mol Genet, 2001, 10(7): 699-703. [24] Liu H, Li X, Ning G, et al. The Machado-Joseph disease deubiquitinase ataxin-3 regulates the stability and apoptotic function of p53[J]. PLoS Biol, 2016, 14(11): e2000733. doi: 10.1371/journal.pbio.2000733. [25] Chen R, Zhang H, Liu P, et al. Gambogenic acid synergistically potentiates bortezomib-induced apoptosis in multiple myeloma[J]. J Cancer, 2017, 8(5): 839-851. [26] Bulbul P, Andrei LG. Proteasome inhibitors induce p53-independent apoptosis in human cancer cells[J]. Am J Pathol, 2011, 178(1): 355-360. [27] Adams J. The development of proteasome inhibitors as anticancer drugs[J]. Cancer Cell, 2004, 5(5): 417-421. [28] Liu X, Roberts J, Dakic A, et al. HPV E7 contributes to the telomerase activity of immortalized and tumorigenic cells and augments E6-induced hTERT promoter function[J]. Virology, 2008, 375(2): 611-623. |
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