Involvement of let-7 microRNA for the therapeutic effects of Rhenium-188-embedded liposomal nanoparticles on orthotopic human head and neck cancer model
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Liang-Ting Lin1,2, Chun-Yuan Chang1, Chih-Hsien Chang3, Hsin-Ell Wang1, Shih-Hwa Chiou2,4,5, Ren-Shyan Liu1, Te-Wei Lee3, Yi-Jang Lee1,6
1Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan
2Department of Medical Research and Education, Taipei Veterans General Hospital, Taipei, Taiwan
3Isotope Application Division, Institute of Nuclear Energy Research, Taoyuan, Taiwan
4Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan
5Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan
6Biophotonics and Molecular Imaging Research Center (BMIRC), National Yang-Ming University, Taipei, Taiwan
Te-Wei Lee, email: [email protected]
Yi-Jang Lee, email: [email protected]
Keywords: 188Re-liposome, HNSCC, orthotopic tumor model, microarray analysis, let-7 microRNA
Received: May 20, 2016 Accepted: August 13, 2016 Published: August 29, 2016
Human head and neck squamous cell carcinoma (HNSCC) is usually treated by surgical resection with adjuvant radio-chemotherapy. In this study, we examined whether the radiopharmaceutical 188Re-liposome could suppress the growth of HNSCC followed by an investigation of molecular mechanisms. The orthotopic HNSCC tumor model was established by human hypopharyngeal FaDu carcinoma cells harboring multiple reporter genes. The drug targeting and therapeutic efficacy of 188Re-liposome were examined using in vivo imaging, bio-distribution, pharmacokinetics, and dosimetry. The results showed that 188Re-liposome significantly accumulated in the tumor lesion compared to free 188Re. The circulation time and tumor targeting of 188Re-liposome were also longer than that of free 188Re in tumor-bearing mice. The tumor growth was suppressed by 188Re-liposome up to three weeks using a single dose treatment. Subsequently, microarray analysis followed by Ingenuity Pathway Analysis (IPA) showed that tumor suppressor let-7 microRNA could be an upstream regulator induced by 188Re-liposome to regulate downstream genes. Additionally, inhibition of let-7i could reduce the effects of 188Re-liposome on suppression of tumor growth, suggesting that let-7 family was involved in 188Re-liposome mediated suppression of tumor growth in vivo. Our data suggest that 188Re-liposome could be a novel strategy for targeting HNSCC partially via induction of let-7 microRNA.
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