Effect of cytokine‑induced killer cells combined with dendritic cells on the survival rate and expression of 14‑3‑3ζ and p‑Bad proteins in Lewis lung cancer cell lines

Hou,Yang; Zang,Dongyu; Li,Xiaoming; Li,Fuzhi

doi:10.3892/ol.2018.8834

Effect of cytokine‑induced killer cells combined with dendritic cells on the survival rate and expression of 14‑3‑3ζ and p‑Bad proteins in Lewis lung cancer cell lines

Authors:
- Yang Hou
- Dongyu Zang
- Xiaoming Li
- Fuzhi Li
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Affiliations: Life Science Institute of Jinzhou Medical University, Jinzhou, Liaoning 121001, P.R. China, Department of Thoraxes Surgery of The Third Affiliated Hospital, Jinzhou Medical University, Jinzhou, Liaoning 121001, P.R. China, Department of Histology and Embryology, Jinzhou Medical University, Jinzhou, Liaoning 121001, P.R. China
Published online on: May 30, 2018 https://doi.org/10.3892/ol.2018.8834
Pages: 1815-1820

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Abstract

In the present study, the function and mechanism of cytokine‑induced killer cells (CIK) combined with dendritic cells (DC‑CIK) were examined in Lewis lung cancer (LLC) cells. Co‑culture of CIK dendritic cells (DC) in vitro was used to investigate their proliferation and the antitumor effects on LLC cells. DC and CIK cells were collected from healthy human peripheral blood mononuclear cells and co‑cultured as an experimental group, while LLC cells were cultured alone as a control group. Cell morphology was observed by an inverted microscope and an MTT assay was utilized to detect the proliferation of LLC cells. Expression of 14‑3‑3ζ and p‑Bad were measured by western blot analysis. Compared with the control group, treatment of LLC cells with DC‑CIK resulted in decreased cell adherence, reduced cell proliferation and abnormal morphological changes. Additionally, DC‑CIK treatment of LLC cells resulted in the decreased expression of 14‑3‑3ζ and p‑Bad protein in LLC cells, which may provide important information pertaining to the possible mechanism of DC‑CIK‑induced antitumor activity against LLC cells. The present study provides a theoretical and experimental basis for the clinical treatment of DC‑CIK cell co‑culture.

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1	Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J and Jemal A: Global cancer statistics, 2012. CA Cancer J Clin. 65:87–108. 2015. View Article : Google Scholar : PubMed/NCBI
2	Sundar R, Soong R, Cho BC, Brahmer JR and Soo RA: Immunotherapy in the treatment of non-small cell lung cancer. Lung Cancer. 85:101–109. 2014. View Article : Google Scholar : PubMed/NCBI
3	Choudhury A, Palma M and Mellstedt H: The future of cancer vaccines for non-small-cell lung cancer: Ongoing trials. Clin Lung Cancer. 9(Suppl 1): S37–S44. 2008. View Article : Google Scholar : PubMed/NCBI
4	Sharma A, Moore WH, Lanuti M and Shepard JA: How I do it: Radiofrequency ablation and cryoablation of lung tumors. J Thorac Imaging. 26:162–174. 2011. View Article : Google Scholar : PubMed/NCBI
5	Schiller JH, Harrington D, Belani CP, Langer C, Sandler A, Krook J, Zhu J and Johnson DH; Eastern Cooperative Oncology Group: Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med. 346:92–98. 2002. View Article : Google Scholar : PubMed/NCBI
6	Koski GK, Cohen PA, Roses RE, Xu S and Czerniecki BJ: Reengineering dendritic cell-based anti-cancer vaccines. Immunol Rev. 222:256–276. 2008. View Article : Google Scholar : PubMed/NCBI
7	Xie S, Wu X, Zhang G, Xu K, Bian X, Zhang S and Ye Y: Remarkable regression of a lung recurrence from an undifferentiated embryonal sarcoma of the liver treated with a DC vaccine combined with immune cells: A case report. Cell Immunol. 290:185–189. 2014. View Article : Google Scholar : PubMed/NCBI
8	Zhao P, Bu X, Wei X, Sun W, Xie X, Li C, Guo Q, Zhu D, Wei X and Gao D: Dendritic cell immunotherapy combined with cytokine-induced killer cells promotes skewing toward Th2 cytokine profile in patients with metastatic non-small cell lung cancer. Int Immunopharmacol. 25:450–456. 2015. View Article : Google Scholar : PubMed/NCBI
9	Shan CC, Shi LR, Ding MQ, Zhu YB, Li XD, Xu B, Jiang JT and Wu CP: Cytokine-induced killer cells co-cultured with dendritic cells loaded with the protein lysate produced by radiofrequency ablation induce a specific antitumor response. Oncol Lett. 9:1549–1556. 2015. View Article : Google Scholar : PubMed/NCBI
10	Zhao M, Li H, Li L and Zhang Y: Effects of a gemcitabine plus platinum regimen combined with a dendritic cell-cytokine induced killer immunotherapy on recurrence and survival rate of non-small cell lung cancer patients. Exp Ther Med. 7:1403–1407. 2014. View Article : Google Scholar : PubMed/NCBI
11	Yang L, Ren B, Li H, Yu J, Cao S, Hao X and Ren X: Enhanced antitumor effects of DC-activated CIKs to chemotherapy treatment in a single cohort of advanced non-small-cell lung cancer patients. Cancer Immunol Immunother. 62:65–73. 2013. View Article : Google Scholar : PubMed/NCBI
12	Tzivion G, Gupta VS, Kaplun L and Balan V: 14-3-3 proteins as potential oncogenes. Semin Cancer Biol. 16:203–213. 2006. View Article : Google Scholar : PubMed/NCBI
13	Neal CL and Yu D: 14-3-3ζ as a prognostic marker and therapeutic target for cancer. Expert Opin Ther Targets. 14:1343–1354. 2010. View Article : Google Scholar : PubMed/NCBI
14	Zhao J, Meyerkord CL, Du Y, Khuri FR and Fu H: 14-3-3 proteins as potential therapeutic targets. Semin Cell Dev Biol. 22:705–712. 2011. View Article : Google Scholar : PubMed/NCBI
15	Fan T, Li R, Todd NW, Qiu Q, Fang HB, Wang H, Shen J, Zhao RY, Caraway NP, Katz RL, et al: Up-regulation of 14-3-3zeta in lung cancer and its implication as prognostic and therapeutic target. Cancer Res. 67:7901–7906. 2007. View Article : Google Scholar : PubMed/NCBI
16	Lowe SW, Cepero E and Evan G: Intrinsic tumour suppression. Nature. 432:307–315. 2004. View Article : Google Scholar : PubMed/NCBI
17	Zha J, Harada H, Yang E, Jockel J and Korsmeyer SJ: Serine phosphorylation of death agonist BAD in response to survival factor results in binding to 14-3-3 not BCL-XL. Cell. 87:619–628. 1996. View Article : Google Scholar : PubMed/NCBI
18	del Peso L, González-García M, Page C, Herrera R and Nuñez G: Interleukin-3-induced phosphorylation of BAD through the protein kinase Akt. Science. 278:687–689. 1997. View Article : Google Scholar : PubMed/NCBI
19	Manegold C, Vansteenkiste J, Cardenal F, Schuette W, Woll PJ, Ulsperger E, Kerber A, Eckmayr J and von Pawel J: Randomized phase II study of three doses of the integrin inhibitor cilengitide versus docetaxel as second-line treatment for patients with advanced non-small-cell lung cancer. Invest New Drugs. 31:175–182. 2013. View Article : Google Scholar : PubMed/NCBI
20	Zhou P, Liang P, Dong B, Yu X, Han Z and Xu Y: Phase I clinical study of combination therapy with microwave ablation and cellular immunotherapy in hepatocellular carcinoma. Cancer Biol Ther. 11:450–456. 2011. View Article : Google Scholar : PubMed/NCBI
21	Lee WC, Wang HC, Hung CF, Huang PF, Lia CR and Chen MF: Vaccination of advanced hepatocellular carcinoma patients with tumor lysate-pulsed dendritic cells: A clinical trial. J Immunother. 28:496–504. 2005. View Article : Google Scholar : PubMed/NCBI
22	Zhu XP, Xu YH, Zhou J and Pan XF: A clinical study evaluating dendritic and cytokine-induced killer cells combined with concurrent radiochemotherapy for stage IIIB non-small cell lung cancer. Genet Mol Res. 14:10228–10235. 2015. View Article : Google Scholar : PubMed/NCBI
23	Cui Y, Yang X, Zhu W, Li J, Wu X and Pang Y: Immune response, clinical outcome and safety of dendritic cell vaccine in combination with cytokine-induced killer cell therapy in cancer patients. Oncol Lett. 6:537–541. 2013. View Article : Google Scholar : PubMed/NCBI
24	Li QY, Shi Y, Huang DH, Yang T, Wang JH, Yan GH, Wang HY, Tang XJ, Xiao CY, Zhang WJ, et al: Cytokine-induced killer cells combined with dendritic cells inhibited liver cancer cells. Int J Clin Exp Med. 8:5601–5610. 2015.PubMed/NCBI
25	Obsil T and Obsilova V: Structural basis of 14-3-3 protein functions. Semin Cell Dev Biol. 22:663–672. 2011. View Article : Google Scholar : PubMed/NCBI
26	Gardino AK and Yaffe MB: 14-3-3 proteins as signaling integration points for cell cycle control and apoptosis. Semin Cell Dev Biol. 22:688–695. 2011. View Article : Google Scholar : PubMed/NCBI
27	Matta A, DeSouza LV, Ralhan R and Siu KW: Small interfering RNA targeting 14-3-3ζ increases efficacy of chemotherapeutic agents in head and neck cancer cells. Mol Cancer Ther. 9:2676–2688. 2010. View Article : Google Scholar : PubMed/NCBI
28	Li Z, Zhao J, Du Y, Park HR, Sun SY, Bernal-Mizrachi L, Aitken A, Khuri FR and Fu H: Down-regulation of 14-3-3zeta suppresses anchorage-independent growth of lung cancer cells through anoikis activation. Proc Natl Acad Sci USA. 105:162–167. 2008. View Article : Google Scholar : PubMed/NCBI
29	Rong F, Li W, Chen K, Li DM, Duan WM, Feng YZ, Li F, Zhou XW, Fan SJ, Liu Y, et al: Knockdown of RhoGDIα induces apoptosis and increases lung cancer cell chemosensitivity to paclitaxel. Neoplasma. 59:541–550. 2012. View Article : Google Scholar : PubMed/NCBI
30	Lin HI, Lee YJ, Chen BF, Tsai MC, Lu JL, Chou CJ and Jow GM: Involvement of Bcl-2 family, cytochrome c and caspase 3 in induction of apoptosis by beauvericin in human non-small cell lung cancer cells. Cancer Lett. 230:248–259. 2005. View Article : Google Scholar : PubMed/NCBI
31	Bishopric NH, Andreka P, Slepak T and Webster KA: Molecular mechanisms of apoptosis in the cardiac myocyte. Curr Opin Pharmacol. 1:141–150. 2001. View Article : Google Scholar : PubMed/NCBI
32	Kavitha K, Kowshik J, Kishore TK, Baba AB and Nagini S: Astaxanthin inhibits NF-κB and Wnt/β-catenin signaling pathways via inactivation of Erk/MAPK and PI3K/Akt to induce intrinsic apoptosis in a hamster model of oral cancer. Biochim Biophys Acta. 1830:4433–4444. 2013. View Article : Google Scholar : PubMed/NCBI
33	Kim MR, Jeong EG, Chae B, Lee JW, Soung YH, Nam SW, Lee JY, Yoo NJ and Lee SH: Pro-apoptotic PUMA and anti-apoptotic phospho-BAD are highly expressed in colorectal carcinomas. Dig Dis Sci. 52:2751–2756. 2007. View Article : Google Scholar : PubMed/NCBI
34	Jeong EG and Lee SH, Kim SS, Ahn CH, Yoo NJ and Lee SH: Immunohistochemical analysis of phospho-BAD protein and mutational analysis of BAD gene in gastric carcinomas. APMIS. 115:976–981. 2007. View Article : Google Scholar : PubMed/NCBI
35	Zippo A, Serafini R, Rocchigiani M, Pennacchini S, Krepelova A and Oliviero S: Histone crosstalk between H3S10ph and H4K16ac generates a histone code that mediates transcription elongation. Cell. 138:1122–1136. 2009. View Article : Google Scholar : PubMed/NCBI