Quinalizarin enhances radiosensitivity of nasopharyngeal carcinoma cells partially by suppressing SHP-1 expression

Pan,Xiaofen; Meng,Rui; Yu,Zhonghua; Mou,Jingjing; Liu,Sha; Sun,Ziyi; Zou,Zhenwei; Wu,Gang; Peng,Gang

doi:10.3892/ijo.2016.3338

Quinalizarin enhances radiosensitivity of nasopharyngeal carcinoma cells partially by suppressing SHP-1 expression

Authors:
- Xiaofen Pan
- Rui Meng
- Zhonghua Yu
- Jingjing Mou
- Sha Liu
- Ziyi Sun
- Zhenwei Zou
- Gang Wu
- Gang Peng
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Affiliations: Oncology Center, Affiliated Hospital of Guangdong Medical College, Zhanjiang, Guangdong 524000, P.R. China, Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China
Published online on: January 14, 2016 https://doi.org/10.3892/ijo.2016.3338
Pages: 1073-1084

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Abstract

The purpose of this study was to investigate the influence of quinalizarin on the radiosensitivity of nasopharyngeal carcinoma (NPC) cells and the relevant underlying mechanisms. Human NPC cell lines CNE-1, CNE-2 and 5-8F were treated with quinalizarin and then irradiated with different X-rays doses. Cell viability, survival, DNA double-strand breaks (DSB), apoptosis, cell cycle distribution, expression of SHP-1 and other related proteins were detected with MTT assay, colony formation assay, immunofluorescent assay, flow cytometry and western blot analysis, respectively. We also examined how the effects of quinalizarin were affected by SHP-1-overexpression by lentivirus transfection. Quinalizarin at 25 µM enhanced radiosensitivity of NPC cells. This increased radiosensitivity was due to inhibition of cell viability, which delayed DSB repair as seen by significantly increased γ-H2AX foci, promoting apoptosis by 34% in CNE-1 and 9% in CNE-2 cells compared to controls and changing cell cycle distribution in CNE-1, but not CNE-2 cells. Quinalizarin treatment obviously decreased SHP-1 protein expression. Overexpressing SHP-1 partially reversed the radiosensitive effect of quinalizarin. Quinalizarin inhibited binding of p65 and the promoter of SHP-1, and decreased the activities of SHP-1 promoter and SHP-1. Quinalizarin enhanced radiosensitivity of NPC cells partially by suppressing SHP-1 expression.

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1	Feng XP, Yi H, Li MY, Li XH, Yi B, Zhang PF, Li C, Peng F, Tang CE, Li JL, et al: Identification of biomarkers for predicting nasopharyngeal carcinoma response to radiotherapy by proteomics. Cancer Res. 70:3450–3462. 2010. View Article : Google Scholar : PubMed/NCBI
2	Iqbal N and Iqbal N: Imatinib: A breakthrough of targeted therapy in cancer. Chemother Res Pract. 2014:3570272014.PubMed/NCBI
3	Sawyers C: Targeted cancer therapy. Nature. 432:294–297. 2004. View Article : Google Scholar : PubMed/NCBI
4	Giamas G, Man YL, Hirner H, Bischof J, Kramer K, Khan K, Ahmed SS, Stebbing J and Knippschild U: Kinases as targets in the treatment of solid tumors. Cell Signal. 22:984–1002. 2010. View Article : Google Scholar : PubMed/NCBI
5	Widmer N, Bardin C, Chatelut E, Paci A, Beijnen J, Levêque D, Veal G and Astier A: Review of therapeutic drug monitoring of anticancer drugs part two - targeted therapies. Eur J Cancer. 50:2020–2036. 2014. View Article : Google Scholar : PubMed/NCBI
6	Trembley JH, Chen Z, Unger G, Slaton J, Kren BT, Van Waes C and Ahmed K: Emergence of protein kinase CK2 as a key target in cancer therapy. Biofactors. 36:187–195. 2010. View Article : Google Scholar : PubMed/NCBI
7	Gao Y and Wang HY: Casein kinase 2 is activated and essential for Wnt/beta-catenin signaling. J Biol Chem. 281:18394–18400. 2006. View Article : Google Scholar : PubMed/NCBI
8	Landesman-Bollag E, Song DH, Romieu-Mourez R, Sussman DJ, Cardiff RD, Sonenshein GE and Seldin DC: Protein kinase CK2: Signaling and tumorigenesis in the mammary gland. Mol Cell Biochem. 227:153–165. 2001. View Article : Google Scholar
9	Trembley JH, Wang G, Unger G, Slaton J and Ahmed K: Protein kinase CK2 in health and disease: CK2: a key player in cancer biology. Cell Mol Life Sci. 66:1858–1867. 2009. View Article : Google Scholar : PubMed/NCBI
10	Hagan CR, Regan TM, Dressing GE and Lange CA: ck2-dependent phosphorylation of progesterone receptors (PR) on Ser81 regulates PR-B isoform-specific target gene expression in breast cancer cells. Mol Cell Biol. 31:2439–2452. 2011. View Article : Google Scholar : PubMed/NCBI
11	Zhu D, Hensel J, Hilgraf R, Abbasian M, Pornillos O, Deyanat-Yazdi G, Hua XH and Cox S: Inhibition of protein kinase CK2 expression and activity blocks tumor cell growth. Mol Cell Biochem. 333:159–167. 2010. View Article : Google Scholar
12	Yefi R, Ponce DP, Niechi I, Silva E, Cabello P, Rodriguez DA, Marcelain K, Armisen R, Quest AF and Tapia JC: Protein kinase CK2 promotes cancer cell viability via up-regulation of cyclooxygenase-2 expression and enhanced prostaglandin E2 production. J Cell Biochem. 112:3167–3175. 2011. View Article : Google Scholar : PubMed/NCBI
13	Olsen BB, Wang SY, Svenstrup TH, Chen BP and Guerra B: Protein kinase CK2 localizes to sites of DNA double-strand break regulating the cellular response to DNA damage. BMC Mol Biol. 13:72012. View Article : Google Scholar : PubMed/NCBI
14	Lin YC, Hung MS, Lin CK, Li JM, Lee KD, Li YC, Chen MF, Chen JK and Yang CT: CK2 inhibitors enhance the radiosensitivity of human non-small cell lung cancer cells through inhibition of stat3 activation. Cancer Biother Radiopharm. 26:381–388. 2011. View Article : Google Scholar : PubMed/NCBI
15	Pagano MA, Bain J, Kazimierczuk Z, Sarno S, Ruzzene M, Di Maira G, Elliott M, Orzeszko A, Cozza G, Meggio F, et al: The selectivity of inhibitors of protein kinase CK2: An update. Biochem J. 415:353–365. 2008. View Article : Google Scholar : PubMed/NCBI
16	Cozza G, Mazzorana M, Papinutto E, Bain J, Elliott M, di Maira G, Gianoncelli A, Pagano MA, Sarno S, Ruzzene M, et al: Quinalizarin as a potent, selective and cell-permeable inhibitor of protein kinase CK2. Biochem J. 421:387–395. 2009. View Article : Google Scholar : PubMed/NCBI
17	Sarno S, de Moliner E, Ruzzene M, Pagano MA, Battistutta R, Bain J, Fabbro D, Schoepfer J, Elliott M, Furet P, et al: Biochemical and three-dimensional-structural study of the specific inhibition of protein kinase CK2 by [5-oxo-5,6-dihy-droindolo-(1,2-a)quinazolin-7-yl]acetic acid (IQA). Biochem J. 374:639–646. 2003. View Article : Google Scholar : PubMed/NCBI
18	Lorenz U: SHP-1 and SHP-2 in T cells: Two phosphatases functioning at many levels. Immunol Rev. 228:342–359. 2009. View Article : Google Scholar : PubMed/NCBI
19	Banville D, Stocco R and Shen SH: Human protein tyrosine phosphatase 1C (PTPN6) gene structure: Alternate promoter usage and exon skipping generate multiple transcripts. Genomics. 27:165–173. 1995. View Article : Google Scholar : PubMed/NCBI
20	Evren S, Wan S, Ma XZ, Fahim S, Mody N, Sakac D, Jin T and Branch DR: Characterization of SHP-1 protein tyrosine phosphatase transcripts, protein isoforms and phosphatase activity in epithelial cancer cells. Genomics. 102:491–499. 2013. View Article : Google Scholar : PubMed/NCBI
21	Nakase K, Cheng J, Zhu Q and Marasco WA: Mechanisms of SHP-1 P2 promoter regulation in hematopoietic cells and its silencing in HTLV-1-transformed T cells. J Leukoc Biol. 85:165–174. 2009. View Article : Google Scholar :
22	Delibrias CC, Floettmann JE, Rowe M and Fearon DT: Downregulated expression of SHP-1 in Burkitt lymphomas and germinal center B lymphocytes. J Exp Med. 186:1575–1583. 1997. View Article : Google Scholar : PubMed/NCBI
23	Oka T, Yoshino T, Hayashi K, Ohara N, Nakanishi T, Yamaai Y, Hiraki A, Sogawa CA, Kondo E, Teramoto N, et al: Reduction of hematopoietic cell-specific tyrosine phosphatase SHP-1 gene expression in natural killer cell lymphoma and various types of lymphomas/leukemias: Combination analysis with cDNA expression array and tissue microarray. Am J Pathol. 159:1495–1505. 2001. View Article : Google Scholar : PubMed/NCBI
24	Sato K, Horiuchi M, Yo R and Nakarai I: A long survival case of small cell lung cancer synchronized with renal cancer]. Kyobu Geka. 44:251–253. 1991.In Japanese. PubMed/NCBI
25	Amin HM, Hoshino K, Yang H, Lin Q, Lai R and Garcia-Manero G: Decreased expression level of SH2 domain-containing protein tyrosine phosphatase-1 (Shp1) is associated with progression of chronic myeloid leukemia. J Pathol. 212:402–410. 2007. View Article : Google Scholar : PubMed/NCBI
26	López-Ruiz P, Rodriguez-Ubreva J, Cariaga AE, Cortes MA and Colás B: SHP-1 in cell-cycle regulation. Anticancer Agents Med Chem. 11:89–98. 2011. View Article : Google Scholar : PubMed/NCBI
27	Peng G, Cao R, Xue J, Li P, Zou Z, Huang J and Ding Q: Increased expression of SHP-1 is associated with local recurrence after radiotherapy in patients with nasopharyngeal carcinoma. Radiol Oncol. 48:40–49. 2014. View Article : Google Scholar : PubMed/NCBI
28	Peng G, Cao RB, Li YH, Zou ZW, Huang J and Ding Q: Alterations of cell cycle control proteins SHP-1/2, p16, CDK4 and cyclin D1 in radioresistant nasopharyngeal carcinoma cells. Mol Med Rep. 10:1709–1716. 2014.PubMed/NCBI
29	Cao R, Ding Q, Li P, Xue J, Zou Z, Huang J and Peng G: SHP1-mediated cell cycle redistribution inhibits radiosensitivity of non-small cell lung cancer. Radiat Oncol. 8:1782013. View Article : Google Scholar : PubMed/NCBI
30	Hall EJ and Giaccia A: Cell survival curves. Radiobiology for the Radiologist. Lippincott Williams & Wilkins; New York, NY: 2011
31	Peng G, Cao RB, Li YH, Zou ZW, Huang J and Ding Q: Alterations of cell cycle control proteins SHP-1/2, p16, CDK4 and cyclin D1 in radioresistant nasopharyngeal carcinoma cells. Mol Med Rep. 10:1709–1716. 2014.PubMed/NCBI
32	Kroonen J, Artesi M, Capraro V, Nguyen-Khac MT, Willems M, Chakravarti A, Bours V and Robe PA: Casein kinase 2 inhibition modulates the DNA damage response but fails to radiosensitize malignant glioma cells. Int J Oncol. 41:776–782. 2012.PubMed/NCBI
33	Liu L, Zou JJ, Luo HS and Wu DH: Effect of protein kinase CK2 gene silencing on radiosensitization in human nasopharyngeal carcinoma cells. Nan Fang Yi Ke Da Xue Xue Bao. 29:1551–1553. 2009.In Chinese. PubMed/NCBI
34	Pan X, Mou J, Liu S, Sun Z, Meng R, Zhou Z, Wu G and Peng G: SHP-1 overexpression increases the radioresistance of NPC cells by enhancing DSB repair, increasing S phase arrest and decreasing cell apoptosis. Oncol Rep. 33:2999–3005. 2015.PubMed/NCBI
35	Wu C, Sun M, Liu L and Zhou GW: The function of the protein tyrosine phosphatase SHP-1 in cancer. Gene. 306:1–12. 2003. View Article : Google Scholar : PubMed/NCBI