Xiaolian Zhang1 
,
Wei Wei1,
LiHong Xia1,
Ruzhen Zheng2
1Department of Radiation Oncology, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003;
2Department of Radiation Oncology, Hangzhou Cancer Hospital, Hangzho, 310002, China.
For correspondence:- Xiaolian Zhang
Email: NCarrenosue@yahoo.com Tel:+8657187236114
Accepted: 28 April 2019
Published: 31 May 2019
Citation:
Zhang X, Wei W, Xia L, Zheng R.
Synergistic effect of radiotherapy and dendritic-cell-based immunotherapy via miR-15b-5p regulation in a colon carcinoma mouse model. Trop J Pharm Res 2019; 18(5):941-948
doi:
10.4314/tjpr.v18i5.5
© 2019 The authors.
This is an Open Access article that uses a funding model which does not charge readers or their institutions for access and distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0) and the Budapest Open Access Initiative (http://www.budapestopenaccessinitiative.org/read), which permit unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited..
Abstract
Purpose: To determine the combined effect of radiotherapy (RT) and dendritic cell (DC)-based immunotherapy on tumor regression, and the influence of miR-15b-5p on the sensitivity of the tumor to RT/DC.
Methods: Colon carcinoma cell line (T-26) was injected subcutaneously into BALB/c mice to generate xenograft tumors. The animals were exposed to radiation therapy (RT) only or DC only, or RT plus DC (RT/DC). Tumor progression was measured and analyzed followed by quantification of miR-15b-5p using qPCR in each group 21 days after tumor inoculation. Overexpressed xenograft tumors were generated by transfecting MiR-15b-5p mimic to CT-26 cell lines and subcutaneously administered to mice. The mice were then subjected to RT/DC treatment and assessed for tumor growth, TUNEL staining, as well as mRNA and protein expressions of B-cell lymphoma-2 (BCL-2), caspase-3 (casp-3), and X-linked inhibitor of apoptosis protein (XIAP).
Results: RT/DC combination treatment resulted in tumor regression and increased miR-15b-5p expression, when compared with other groups treated with RT and DC alone (p < 0.001). There was a marked reduction in tumor growth following RT/DC combination therapy in miR-15b-5p overexpressed xenograft tumor (p < 0.001). Moreover, miR-15b-5p/(RT/DC) treatment significantly increased cancer cell apoptosis. These results were substantiated by increased mRNA and protein expressions of casp-3, reduced BCL-2 and XIAP (p < 0.001).
Conclusion: These findings demonstrate that RT/DC combination therapy increases miR-15b-5p levels in mice, and that miR-15b-5p upregulation enhances the sensitivity of tumors to RT/DC combination therapy. Therefore, the combination of RT and dendritic cell-based immunotherapy offers significant therapeutic advantage in controlling cancers, including metastatic tumors.
Keywords: Radiotherapy, Dendritic cells, Colon carcinoma, Apoptosis, MiR-15b-5p
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