JNK pathway inhibition enhances chemotherapeutic sensitivity to Adriamycin in nasopharyngeal carcinoma cells

Liu,Yong; Feng,Jing; Zhao,Ming; Wu,Jingbo; Fan,Juan; Wen,Qinglian; Xu,Jinhui; Zhang,Jianwen; Fu,Shaozhi; Wang,Biqiong; Lu,Yun; Xiong,Kang; Xiang,Li; Zhang,Yanling; Yang,Linglin

doi:10.3892/ol.2017.6349

August-2017 Volume 14 Issue 2

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August-2017 Volume 14 Issue 2

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Article

JNK pathway inhibition enhances chemotherapeutic sensitivity to Adriamycin in nasopharyngeal carcinoma cells

Authors:
- Yong Liu
- Jing Feng
- Ming Zhao
- Jingbo Wu
- Juan Fan
- Qinglian Wen
- Jinhui Xu
- Jianwen Zhang
- Shaozhi Fu
- Biqiong Wang
- Yun Lu
- Kang Xiong
- Li Xiang
- Yanling Zhang
- Linglin Yang
View Affiliations / Copyright

Affiliations: Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, P.R. China
Pages: 1790-1794
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Published online on: June 8, 2017

https://doi.org/10.3892/ol.2017.6349
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Abstract

The role of c-Jun N-terminal kinases (JNKs) in the pathogenesis of cancer is well‑known due to their involvement in carcinogenesis. Although previous studies have discussed different functions of JNKs depending on cell type, the present study aimed to investigate the function of JNKs in nasopharyngeal carcinoma (NPC) cells, as well as their involvement in chemotherapy sensitivity to Adriamycin. The present results showed that Adriamycin administration reduced cell viability and led to elevated expressions of c‑Jun, phosphorylated JNK and phosphorylated c‑Jun, indicating an activated JNK pathway. Notably, JNK inhibition by SP600125 also reduced cell growth. Thus, Adriamycin treatment combined with SP600125 was more effective on cell growth inhibition than each agent alone. The apoptosis analysis confirmed the reduction in cell growth. Therefore, these data provide evidence that the JNK pathway activity is negatively associated with cell viability, and its decline could sensitize NPC cells to Adriamycin.

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1	Zhang F and Zhang J: Clinical hereditary characteristics in nasopharyngeal carcinoma through Ye-Liang's family cluster. Chin Med J (Engl). 112:185–187. 1999.PubMed/NCBI
2	Li XJ, Ong CK, Cao Y, Xiang YQ, Shao JY, Ooi A, Peng LX, Lu WH, Zhang Z, Petillo D, et al: Serglycin is a theranostic target in nasopharyngeal carcinoma that promotes metastasis. Cancer Res. 71:3162–3172. 2011. View Article : Google Scholar : PubMed/NCBI
3	Lee AW, Lin JC and Ng WT: Current management of nasopharyngeal cancer. Semin Radiat Oncol. 22:233–244. 2012. View Article : Google Scholar : PubMed/NCBI
4	Zhang L, Chen QY, Liu H, Tang LQ and Mai HQ: Emerging treatment options for nasopharyngeal carcinoma. Drug Des Devel Ther. 7:37–52. 2013.PubMed/NCBI
5	Chang PY, Wu ZZ, Sun NK and Chao CC: EBV-encoded LMP-1 sensitizes nasopharyngeal carcinoma cells to genotoxic drugs by down-regulating Cabin1 expression. J Cell Physiol. 229:309–322. 2014. View Article : Google Scholar : PubMed/NCBI
6	Johnson GL and Lapadat R: Mitogen-activated protein kinase pathways mediated by ERK, JNK, and p38 protein kinases. Science. 298:1911–1923. 2002. View Article : Google Scholar : PubMed/NCBI
7	Kyriakis JM and Avruch J: Mammalian MAPK signal transduction pathways activated by stress and inflammation: A 10-year update. Physiol Rev. 92:689–737. 2012. View Article : Google Scholar : PubMed/NCBI
8	Vlahopoulos S and Zoumpourlis VC: JNK: A key modulator of intracellular signaling. Biochemistry (Mosc). 69:844–854. 2004. View Article : Google Scholar : PubMed/NCBI
9	Hibi M, Lin A, Smeal T, Minden A and Karin M: Identification of an oncoprotein- and UV-responsive protein kinase that binds and potentiates the c-Jun activation domain. Genes Dev. 7:2135–2148. 1993. View Article : Google Scholar : PubMed/NCBI
10	Gupta S, Campbell D, Dérijard B and Davis RJ: Transcription factor ATF2 regulation by the JNK signal transduction pathway. Science. 267:389–393. 1995. View Article : Google Scholar : PubMed/NCBI
11	Cavigelli M, Dolfi F, Claret FX and Karin M: Induction of c-fos expression through JNK-mediated TCF/Elk-1 phosphorylation. EMBO J. 14:5957–5964. 1995.PubMed/NCBI
12	Tournier C: The 2 Faces of JNK Signaling in Cancer. Genes Cancer. 4:397–400. 2013. View Article : Google Scholar : PubMed/NCBI
13	Shibata W, Maeda S, Hikiba Y, Yanai A, Sakamoto K, Nakagawa H, Ogura K, Karin M and Omata M: c-Jun NH2-terminal kinase 1 is a critical regulator for the development of gastric cancer in mice. Cancer Res. 68:5031–5039. 2008. View Article : Google Scholar : PubMed/NCBI
14	Nateri AS, Spencer-Dene B and Behrens A: Interaction of phosphorylated c-Jun with TCF4 regulates intestinal cancer development. Nature. 437:281–285. 2005. View Article : Google Scholar : PubMed/NCBI
15	Cellurale C, Weston CR, Reilly J, Garlick DS, Jerry DJ, Sluss HK and Davis RJ: Role of JNK in a Trp53-dependent mouse model of breast cancer. PLoS One. 5:e124692010. View Article : Google Scholar : PubMed/NCBI
16	Cellurale C, Girnius N, Jiang F, Cavanagh-Kyros J, Lu S, Garlick DS, Mercurio AM and Davis RJ: Role of JNK in mammary gland development and breast cancer. Cancer Res. 72:472–481. 2012. View Article : Google Scholar : PubMed/NCBI
17	Winn RA, Marek L, Han SY, Rodriguez K, Rodriguez N, Hammond M, Van Scoyk M, Acosta H, Mirus J, Barry N, et al: Restoration of Wnt-7a expression reverses non-small cell lung cancer cellular transformation through frizzled-9-mediated growth inhibition and promotion of cell differentiation. J Biol Chem. 280:19625–19634. 2005. View Article : Google Scholar : PubMed/NCBI
18	Kim R, Ohi Y, Inoue H and Toge T: Enhancement of chemotherapeutic agents induced-apoptosis associated with activation of c-Jun N-terminal kinase 1 and caspase 3 (CPP32) in bax-transfected gastric cancer cells. Anticancer Res. 20:439–444. 2000.PubMed/NCBI
19	Levresse V, Marek L, Blumberg D and Heasley LE: Regulation of platinum-compound cytotoxicity by the c-Jun N-terminal kinase and c-Jun signaling pathway in small-cell lung cancer cells. Mol Pharmacol. 62:689–697. 2002. View Article : Google Scholar : PubMed/NCBI
20	Vadlapatla RK, Vadlapudi AD, Pal D and Mitra AK: Mechanisms of drug resistance in cancer chemotherapy: Coordinated role and regulation of efflux transporters and metabolizing enzymes. Curr Pharm Des. 19:7126–7140. 2013. View Article : Google Scholar : PubMed/NCBI
21	Lin L, Deng W, Tian Y, Chen W, Wang J, Fu L, Shi D, Zhao M and Luo W: Lasiodin inhibits proliferation of human nasopharyngeal carcinoma cells by simultaneous modulation of the Apaf-1/caspase, AKT/MAPK and COX-2/NF-κB signaling pathways. PLoS One. 9:e977992014. View Article : Google Scholar : PubMed/NCBI
22	Chou J, Lin YC, Kim J, You L, Xu Z, He B and Jablons DM: Nasopharyngeal carcinoma-review of the molecular mechanisms of tumorigenesis. Head Neck. 30:946–963. 2008. View Article : Google Scholar : PubMed/NCBI
23	Kyriakis JM and Avruch J: Mammalian mitogen-activated protein kinase signal transduction pathways activated by stress and inflammation. Physiol Rev. 81:807–869. 2001.PubMed/NCBI

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

JNK pathway inhibition enhances chemotherapeutic sensitivity to Adriamycin in nasopharyngeal carcinoma cells

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