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山东大学学报(医学版) ›› 2017, Vol. 55 ›› Issue (11): 1-6.doi: 10.6040/j.issn.1671-7554.0.2016.1425

• 基础医学 •    下一篇

磷脂酰肌醇-4-磷酸酶II型对宫颈癌细胞增殖及凋亡的影响

孙泽雨1,陈颖1,林家香2,刘娟1,赵蔚明1   

  1. 山东大学基础医学院 1. 病原生物学系;2.病理学系, 山东 济南 250012
  • 收稿日期:2016-11-03 出版日期:2017-11-10 发布日期:2017-11-10
  • 通讯作者: 赵蔚明. E-mail:zhaowm@sdu.edu.cn E-mail:zhaowm@sdu.edu.cn
  • 基金资助:
    国家自然科学基金(81472552)

Influence of inositol polyphosphate-4-phosphatase type II on the proliferation and apoptosis of cervical cancer cells

SUN Zeyu1, CHEN Ying1, LIN Jiaxiang2, LIU Juan1, ZHAO Weiming1   

  1. 1. Department of Pathogenic Biology;
    2. Department of Pathology, School of Basic Medical Sciences, Shandong University, Jinan 250012, Shandong, China
  • Received:2016-11-03 Online:2017-11-10 Published:2017-11-10

摘要: 目的 探讨磷脂酰肌醇-4-磷酸酶II型(INPP4B)对宫颈癌细胞生长增殖、细胞周期及凋亡的影响。 方法 Western blotting检测常见的宫颈癌细胞系中INPP4B的基础表达水平,对INPP4B阴性的SiHa、C33a细胞转染表达质粒LHCX-INPP4B,高表达INPP4B的CaSki细胞转染INPP4B特异性的siRNA,Western blotting检测细胞中INPP4B表达的变化。CCK-8、克隆形成实验检测INPP4B对宫颈癌细胞生长增殖的影响;BrdU染色检测细胞周期,Annexin V-FITC/PI双染后流式细胞仪检测细胞凋亡。 结果 CCK-8和克隆形成实验显示,过表达INPP4B使SiHa和C33a细胞的活性和克隆形成能力明显下降(P均<0.05); BrdU实验表明,转染INPP4B后SiHa细胞和C33a细胞进入S期的比例减少(P=0.04,P=0.01)。与之相应,干扰INPP4B表达后CaSki细胞的生长增殖能力增强,进入S期的细胞比例增加(P<0.01)。但INPP4B表达的变化对SiHa、C33a和CaSki细胞的凋亡无明显影响。 结论 INPP4B可抑制宫颈癌细胞的生长增殖和细胞周期进程。

关键词: 宫颈癌, 磷脂酰肌醇-4-磷酸酶II型, 周期, 增殖

Abstract: Objective To study the effect of inositol polyphosphate-4-phosphatase type II(INPP4B)on the proliferation,cell cycle and apoptosis of cervical cancer cells. Methods Western blotting was employed to detect basic expression of INPP4B in various kinds of cervical cancer cell lines. The INPP4B expressions in LHCX-INPP4B transfected SiHa and C33a cells as well as INPP4B specific siRNA transfected CaSki cells were determined by Western blotting. CCK-8 and colony formation assay were used to test cell growth and proliferation. Cell cycle was detected by using BrdU assay. Cell apoptosis was evaluated using Annexin V-FITC/PI cell apoptosis kit. Results CCK-8 and clone formation assay showed that the overexpression of INPP4B significantly reduced the cell viability and clonogenic ability of SiHa and C33a(all P<0.05). BrdU assay showed that the proportion of SiHa and C33a cells in S phase decreased after being transfected with INPP4B(P=0.04, P=0.01). Accordantly, depletion of INPP4B in Caski cells increased cell viability and the percentage of the cells entering S phase(P<0.01). However, INPP4B did not influence the apoptosis of cervical cancer cells. Conclusion INPP4B inhibits the growth and proliferation of cervical cancer cells and leads to cell cycle arrest.

Key words: Inositol polyphosphate-4-phosphatase type II, Cycle, Cervical cancer, Proliferation

中图分类号: 

  • R737
[1] Parkin DM, Bray F, Ferlay J, et al. Global cancer statistics, 2002[J]. CA Cancer J Clin, 2005, 55(2):74-108.
[2] Snijders PJ, Steenbergen RD, Heideman DA, et al. HPV-mediated cervical carcinogenesis: concepts and clinical implications[J]. J Pathol, 2006, 208(2):152-164.
[3] Walboomers JM, Jacobs MV, Manos MM, et al. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide [J]. J Pathol, 1999, 189(1):12-19.
[4] Münger K, Baldwin A, Edwards KM, et al. Mechanisms of human papillo mavirus induced oncogenesis[J]. J Virol, 2004, 78(21):11451-11460.
[5] Vivanco I, Sawyers C. The phosphatidylinositol 3-kinase-AKT pathway in human cancer[J]. Nat Rev Cancer, 2002, 2(7):489-501.
[6] Vara J, Casado E, de Castro J, et al. PI3K/AKT signaling pathway and cancer[J]. Cancer Treat Rev, 2004, 30(2):193-204.
[7] Fruman DA, Rommel C. PI3K and cancer: lessons, challenges and opportunities[J]. Nat Rev Drug Discov, 2014, 13(2):140-156.
[8] Li Chew C, Lunardi A, Gulluni F, et al. In Vivo role of INPP4B in tumor and metastasis suppression throμgh regulation of PI3K-AKT signaling at endosomes[J]. Cancer Discov, 2015, 5(7):740-751.
[9] Guo ST, Chi MN, Yang RH, et al. INPP4B is an oncogenic regulator in human colon cancer[J]. Oncogene, 2016, 35(23):3049-3061.
[10] Gasser JA, Inuzuka H, Lau AW, et al. SGK3 mediates INPP4B-dependent PI3K signaling in breast cancer[J]. Mol Cell, 2014, 56(4):595-607.
[11] Sowalsky AG, Xia Z, Wang L, et al. Whole transcriptome sequencing reveals extensive unspliced mRNA in metastatic castration-resistant prostate cancer[J]. Mol Cancer Res, 2015, 13(1):98-106.
[12] Bertucci MC, Mitchell CA. Phosphoinositide 3-kinase and INPP4B in human breast cancer[J]. Ann N Y Acad Sci, 2013, 1280:1-5. doi:10.1111/nyas.12036.
[13] Manzano RG, Martinez-Navarro EM, Forteza J, et al. Microarray phosphatome profiling of breast cancer patients unveils a complex phosphatase regulatory role of the MAPK and PI3K pathways in estrogen receptor-negative breast cancers[J]. Int J Oncol, 2014, 45(6): 2250-2266.
[14] Lee JJ, Loh K, Yap YS. PI3K/Akt/mTOR inhibitors in breast cancer[J]. Cancer biology & medicine, 2015, 12(4):342-354.
[15] Sun Y, Ding H, Liu X, et al. INPP4B overexpression enhances the antitumor efficacy of PARP inhibitor AG014699 in MDA-MB-231 triple-negative breast cancer cells[J]. Tumour Biol, 2014, 35(5):4469-4477.
[16] Bruhn MA, Pearson RB, Hannan RD, et al. AKT-independent PI3-K signaling in cancer-emerging role for SGK3[J]. Cancer Manag Res, 2013,5:281-292. doi: 10.2147/CMAR.S35178. eCollection, 2013.
[17] Rijal S, Fleming S, Cummings N, et al. Inositol polyphosphate 4-phosphatase II(INPP4B)is associated with chemoresistance and poor outcome in AML[J]. Blood, 2015, 125(18):2815-2824.
[18] Agoulnik IU, Hodgson MC, Bowden WA, et al. INPP4B: the new kid on the PI3K block[J]. Oncotarget, 2011, 2(4):321-328.
[19] Ferron M, Vacher J. Characterization of the murine Inpp4b gene and identification of a novel isoform[J].Gene, 2006, 376(1):152-161.
[20] Weaver BA. Epidemiology and natural history of genital human papillomavirus infection[J]. J Am Osteopath Assoc, 2006,106(3 Suppl 1):S2-8.
[21] Werness BA, Levine AJ, Howley PM. Association of human papillomavirus types 16 and 18 E6 proteins with p53[J]. Science, 1990, 248(4951):76-79.
[22] Chen J. Signaling pathways in HPV-associated cancers and therapeutic implications[J]. Reviews in medical virology, 2015(Suppl 1):24-53. doi:10.1002/rmv.1823.
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