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MiR-375 and Doxorubicin Co-delivered by Liposomes for Combination Therapy of Hepatocellular Carcinoma
Doxorubicin (DOX) is one of the most frequently used anti-cancer drugs and the front line option for hepatocellular carcinoma (HCC) treatment. However, the clinical applications of DOX are restricted largely due to its toxicity and chemoresistance. Here, we report that miR-375 and DOX were co-delive...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society of Gene & Cell Therapy
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5415965/ https://www.ncbi.nlm.nih.gov/pubmed/28624193 http://dx.doi.org/10.1016/j.omtn.2017.03.010 |
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author | Fan, Yin-Ping Liao, Jia-Zhi Lu, Ya-Qi Tian, De-An Ye, Feng Zhao, Peng-Xuan Xiang, Guang-Ya Tang, Wang-Xian He, Xing-Xing |
author_facet | Fan, Yin-Ping Liao, Jia-Zhi Lu, Ya-Qi Tian, De-An Ye, Feng Zhao, Peng-Xuan Xiang, Guang-Ya Tang, Wang-Xian He, Xing-Xing |
author_sort | Fan, Yin-Ping |
collection | PubMed |
description | Doxorubicin (DOX) is one of the most frequently used anti-cancer drugs and the front line option for hepatocellular carcinoma (HCC) treatment. However, the clinical applications of DOX are restricted largely due to its toxicity and chemoresistance. Here, we report that miR-375 and DOX were co-delivered by liposomes (named L-miR-375/DOX-NPs) for combination therapy of HCC and drug resistance reversion of DOX. In vitro, L-miR-375/DOX-NPs could deliver DOX and miR-375 efficiently and simultaneously into HCC cells and ensure the successful release of mature miR-375 and DOX. Then, the released miR-375 suppressed the malignant hallmarks of HCC by significantly decreasing the expression of AEG-1, YAP1, and ATG7, while the released DOX evidently accelerated cell apoptosis and blocked cycle at a G2/M stage by activating the P53/Bax/Bcl-2, caspase-3, and P-JNK, P-P38 pathway. Furthermore, miR-375 dramatically inhibited drug resistance of DOX by reducing the expression of multidrug resistance gene 1 (MDR1). In vivo, L-miR-375/DOX-NPs exhibited enhanced anti-tumor efficiency in xenograft HCC mouse models with mild adverse effects compared with doxorubicin or miR-375 alone. In conclusion, our research demonstrated that L-miR-375/DOX-NPs had significant synergetic anti-tumor effects and added values in overcoming drug resistance, which may represent a promising approach for the therapy of HCC. |
format | Online Article Text |
id | pubmed-5415965 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | American Society of Gene & Cell Therapy |
record_format | MEDLINE/PubMed |
spelling | pubmed-54159652017-05-05 MiR-375 and Doxorubicin Co-delivered by Liposomes for Combination Therapy of Hepatocellular Carcinoma Fan, Yin-Ping Liao, Jia-Zhi Lu, Ya-Qi Tian, De-An Ye, Feng Zhao, Peng-Xuan Xiang, Guang-Ya Tang, Wang-Xian He, Xing-Xing Mol Ther Nucleic Acids Original Article Doxorubicin (DOX) is one of the most frequently used anti-cancer drugs and the front line option for hepatocellular carcinoma (HCC) treatment. However, the clinical applications of DOX are restricted largely due to its toxicity and chemoresistance. Here, we report that miR-375 and DOX were co-delivered by liposomes (named L-miR-375/DOX-NPs) for combination therapy of HCC and drug resistance reversion of DOX. In vitro, L-miR-375/DOX-NPs could deliver DOX and miR-375 efficiently and simultaneously into HCC cells and ensure the successful release of mature miR-375 and DOX. Then, the released miR-375 suppressed the malignant hallmarks of HCC by significantly decreasing the expression of AEG-1, YAP1, and ATG7, while the released DOX evidently accelerated cell apoptosis and blocked cycle at a G2/M stage by activating the P53/Bax/Bcl-2, caspase-3, and P-JNK, P-P38 pathway. Furthermore, miR-375 dramatically inhibited drug resistance of DOX by reducing the expression of multidrug resistance gene 1 (MDR1). In vivo, L-miR-375/DOX-NPs exhibited enhanced anti-tumor efficiency in xenograft HCC mouse models with mild adverse effects compared with doxorubicin or miR-375 alone. In conclusion, our research demonstrated that L-miR-375/DOX-NPs had significant synergetic anti-tumor effects and added values in overcoming drug resistance, which may represent a promising approach for the therapy of HCC. American Society of Gene & Cell Therapy 2017-04-06 /pmc/articles/PMC5415965/ /pubmed/28624193 http://dx.doi.org/10.1016/j.omtn.2017.03.010 Text en © 2017 The Author(s) http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Original Article Fan, Yin-Ping Liao, Jia-Zhi Lu, Ya-Qi Tian, De-An Ye, Feng Zhao, Peng-Xuan Xiang, Guang-Ya Tang, Wang-Xian He, Xing-Xing MiR-375 and Doxorubicin Co-delivered by Liposomes for Combination Therapy of Hepatocellular Carcinoma |
title | MiR-375 and Doxorubicin Co-delivered by Liposomes for Combination Therapy of Hepatocellular Carcinoma |
title_full | MiR-375 and Doxorubicin Co-delivered by Liposomes for Combination Therapy of Hepatocellular Carcinoma |
title_fullStr | MiR-375 and Doxorubicin Co-delivered by Liposomes for Combination Therapy of Hepatocellular Carcinoma |
title_full_unstemmed | MiR-375 and Doxorubicin Co-delivered by Liposomes for Combination Therapy of Hepatocellular Carcinoma |
title_short | MiR-375 and Doxorubicin Co-delivered by Liposomes for Combination Therapy of Hepatocellular Carcinoma |
title_sort | mir-375 and doxorubicin co-delivered by liposomes for combination therapy of hepatocellular carcinoma |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5415965/ https://www.ncbi.nlm.nih.gov/pubmed/28624193 http://dx.doi.org/10.1016/j.omtn.2017.03.010 |
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