title: MiR-101 and doxorubicin codelivered by liposomes suppressing malignant properties of hepatocellular carcinoma.
abstract: 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.
authors.affiliation: Institute of Liver Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Xu
authors.affiliation: Institute of Liver Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Jia-Zhi
authors.initials: JZ
authors.lastname: Liao
authors.affiliation: School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Guang-Ya
authors.initials: GY
authors.lastname: Xiang
authors.affiliation: School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Peng-Xuan
authors.initials: PX
authors.lastname: Zhao
authors.affiliation: Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Ye
authors.affiliation: Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan, China.
authors.forename: Qiu
authors.initials: Q
authors.lastname: Zhao
authors.affiliation: Institute of Liver Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Xing-Xing
authors.identifier: 0000-0003-0001-8473
authors.initials: XX
authors.lastname: He
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003131:Combined Modality Therapy; D004317:Doxorubicin / Q000008:administration & dosage* / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D008081:Liposomes; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000008:administration & dosage* / Q000494:pharmacology; D053758:Nanoparticles; D016896:Treatment Outcome; D023041:Xenograft Model Antitumor Assays
chemical_list: D000903:Antibiotics, Antineoplastic; D008081:Liposomes; C534072:MIRN101 microRNA, human; D035683:MicroRNAs; D004317:Doxorubicin
keywords: Combination therapy; doxorubicin; liposome nanoparticles; liver cancer; microRNA