期刊
CANCER MEDICINE
卷 6, 期 3, 页码 651-661出版社
WILEY
DOI: 10.1002/cam4.1016
关键词
Combination therapy; doxorubicin; liposome nanoparticles; liver cancer; microRNA
类别
资金
- National Natural Science Foundation of China [81472832]
- Natural Science Foundation of Hubei Province [2014CFB443]
- Youth Sciences and Technology Chenguang Planning of Wuhan [2014070404010219]
- Outstanding Youth Science Foundation of Tongji Hospital [YXQN005]
- Fundamental Research Funds for the Central Universities [2014QN084]
MiR-101, an important tumor-suppressive microRNA (miRNA) in hepatocellular carcinoma (HCC), has been affirmed significantly downregulated in HCC and participated in promoting apoptosis, decreasing proliferation and invasiveness of HCC cells, as well as increasing sensitivity of chemotherapeutic drug. However, miR-101-based combination therapies with doxorubicin (DOX) are not reported yet. Recently, nanomaterials-based approaches, especially liposome formulations, have been approved for clinical use and seem to provide a great opportunity to codeliver therapeutic agents for cancer therapy. In this study, we have successfully prepared liposome (L) nanoparticles to efficiently deliver miR-101 and DOX to HCC cells simultaneously. The effects of codelivery system miR-101/doxorubicin liposome (miR-101/DOX-L) on tumor malignant phenotypes of HCC cells were evaluated through analyzing cell proliferation, colony formation, cell migration, cell invasion, cell apoptosis assay, and the expression of related genes. In subcutaneous xenografts developed by HCC cells, the inhibition of tumor growth was analyzed through gross morphology, growth curve, proliferation marker Ki-67, apoptosis signals, and the expression of related genes. These experiments demonstrated that miR-101/DOX-L inhibited tumor properties of liver cancer cells in vitro and in vivo through targeting correlative genes by combinatory role of miR-101 and DOX. In conclusion, our results indicated that liposome nanoparticle is a reliable delivery strategy to codeliver miR-101 and DOX simultaneously, and miR-101-and DOX-based combination therapy can result in significant synergetic antitumor effects in vivo and vitro.
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