Journal of Shandong University (Health Sciences) ›› 2018, Vol. 56 ›› Issue (1): 70-75.doi: 10.6040/j.issn.1671-7554.0.2017.138

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Effects of proteasome inhibitor bortezomib combined with cisplatin on proliferation of human cervical cancer cells

DING Changkuan, Jason Chen   

  1. Cancer Research Centre of Shandong University, Jinan 250012, Shandong, China
  • Published:2022-09-27

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Abstract: Objective To investigate the effects of proteasome inhibitor bortezomib(BTZ), cisplatin(CIS)and their combination on proliferation of cervical cancer cells and to explore the mechanisms involved. Methods Hela cells were divided into four groups: normal control group(NC group), BTZ group, CIS group and C&B group. Cell Counting Kit-8(CCK-8)was used to examine HeLa cell proliferation after treatment. Western blotting was used to investigate the expression of p53 protein and Rb protein in the treated cells. Flow cytometry was used to observe apoptosis ratio after treatment. Results The inhibitory effect on the proliferation of HeLa cells in the C&B group was higher compared with the other groups. Western blotting analysis showed that the expression of p53 protein in CIS group was higher than that in NC group and C&B group(P<0.05), but had no obvious difference in BTZ group. Compared with that in other three groups, the expression of Rb protein in BTZ group was higher(P<0.05), and no obvious change was observed among these three groups. Flow cytometry demonstrated a synergistic effect of BTZ and CIS on HeLa cell apoptosis. Conclusion CIS may inhibit the proliferation of HeLa cells via regulating the expression of p53; BTZ may inhibit the proliferation of HeLa cells via regulating the expression of Rb; BTZ could enhance the inhibitory effects of CIS on HeLa cells.

Key words: Proteasome inhibitor, Bortezomib, Cisplatin, p53 protein, Rb protein, Hela cell, Ceivical cancer

CLC Number: 

  • R741.05
[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 cant 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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