MiR‐101 and doxorubicin codelivered by liposomes suppressing malignant properties of hepatocellular carcinoma

• Published in: Cancer medicine (Malden, MA) Vol. 6; no. 3; pp. 651 - 661
• Main Authors: Xu, Fei, Liao, Jia‐Zhi, Xiang, Guang‐Ya, Zhao, Peng‐Xuan, Ye, Feng, Zhao, Qiu, He, Xing‐Xing
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01.03.2017; John Wiley and Sons Inc
• Subjects: Animals; Antibiotics, Antineoplastic - administration & dosage; Antibiotics, Antineoplastic - pharmacology; Antitumor activity; Apoptosis; Cancer Biology; Cancer therapies; Carcinoma, Hepatocellular - drug therapy; Carcinoma, Hepatocellular - genetics; Cell adhesion & migration; Cell cycle; Cell growth; Cell Line, Tumor; Cell migration; Cell proliferation; Cell Proliferation - drug effects; Cell Survival - drug effects; Combination therapy; Combined Modality Therapy; Cytology; Doxorubicin; Doxorubicin - administration & dosage; Doxorubicin - pharmacology; Drug delivery systems; Drugs; Experiments; Gene Expression Regulation, Neoplastic - drug effects; Hep G2 Cells; Hepatocellular carcinoma; Hepatocytes; Humans; Invasiveness; Laboratory animals; liposome nanoparticles; Liposomes; Liver cancer; Liver Neoplasms - drug therapy; Liver Neoplasms - genetics; Male; Melanoma; Mice; microRNA; MicroRNAs; MicroRNAs - administration & dosage; MicroRNAs - pharmacology; miRNA; Nanoparticles; Nanotechnology; Original Research; Phenotypes; Studies; Treatment Outcome; Xenograft Model Antitumor Assays; Xenografts; Beijing China; China; microRNA; liver cancer; doxorubicin; Combination therapy; liposome nanoparticles
• DOI: 10.1002/cam4.1016
• ISSN: 2045-7634

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. We first prepared liposome nanoparticles to codeliver miR‐101 and doxorubicin (DOX) for combinatory therapy in hepatocellular carcinoma (HCC), 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.