Combining TGF-β1 knockdown and miR200c administration to optimize antitumor efficacy of B16F10/GPI-IL-21 vaccine
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Xiaoying Wang1,*, Fengshu Zhao1,*, Xiangfeng He1,2,*, Jing Wang3, Ying Zhang1, Hongyi Zhang1, Yaoyao Ni1, Jianan Sun1, Xiaobing Wang4 and Jun Dou1
1 Department of Pathogenic Biology and Immunology, School of Medicine & Collaborative Innovation Center of Suzhou Nano Science and Technology, Southeast University, Nanjing, China
2 Department of Medical Oncology, Affiliated Tumor Hospital of Nantong University, Nantong, China
3 Department of Gynecology and Obstetrics, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
4 Department of Center for Experiment Animal, School of Medicine, Southeast University, Nanjing, China
* These authors have equally contributed to this work
Jun Dou, email:
Fengshu Zhao, email:
Keywords: melanoma, tumor vaccine, interleukin-21, transforming growth factor β1, miR200c
Received: February 03, 2015 Accepted: March 05, 2015 Published: March 30, 2015
TGF-β1 secreted abundantly by tumors cells as well as present in the local microenvironment promotes neoplasm invasion and metastasis by triggering the epithelial to mesenchymal transition (EMT). MiR200c has been shown to suppress EMT and to regulate the cellular epithelial and interstitial state conversion, whereas the tumor vaccines are intended to specifically initiate or amplify a host response against evolving tumor cells. Our study aimed at optimizing the antitumor effects of the B16F10/glycosylphosphatidylinositol-interleukin 21 (B16F10/GPI-IL-21) tumor vaccine on melanoma bearing mice by combining the TGF-β1 knockdown and the administration of miR200c agomir. The mice were subcutaneously vaccinated with inactivated B16F10/GPI-IL-21 vaccine and challenged by B16F10 cells transfected with shTGF-β1 (B16F10/shTGF-β1 cells) or B16F10/shTGF-β1 cells with the administration of miR200c agomir. The later combination showed that, when compared with the mice in the control group that received no vaccination, vaccinated mice significantly increased NK and CTL activities, enhanced levels of IFN-γ, and reduced expression of TGF-β1, N-cadherin, Vimentin, Gli1/2, P-Smad2/3 and others involved in promoting expression of EMT-related molecules in tumor areas, and inhibited the melanoma metastasis in lungs and lymph nodes. Altogether, our findings demonstrate that this synergistic anti-cancer regimen effectively induces strong immune response and diminishes the melanoma progression.
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