title: Delivery of sFIT-1 engineered MSCs in combination with a continuous low-dose doxorubicin treatment prevents growth of liver cancer.
abstract: One important process in liver cancer growth and progression is angiogenesis. Vascular endothelial growth factor (VEGF) has the significant role in liver cancer angiogenesis. sFlt1 (soluble Fms-like tyrosine kinase-1) is the promising inhibitor of VEGF and can be used as the new method of inhibiting angiogenesis. MSCs (Mesenchymal stem cells) can infiltrate into tumor tissue and function as the efficient transgene delivery mediator. Here, we engineered murine MSCs to express sFlt1 and examined the anti-tumor effect of MSC- sFlt1 in combination with continues low-dose doxorubicin treatment. We found that this combination therapy significantly inhibited liver cancer cells proliferation. Above all, HepG2 xenografts treated with this combination therapy went into remission. It is of note that this inhibition effect was not p53 binding and by increasing caspase8. This study suggests that this combination treatment has novel therapeutic potential for liver cancer because of significantly inhibiting cancer cells growth and anti-angiogenesis in vitro and in vivo.
authors.affiliation: General Surgery of the Hospital Affiliated Hospital of Xuzhou Medical University, Digestive Disease Research Laboratory of Xuzhou Medical University, Xuzhou, Jiangsu 221002, PR China.
authors.forename: Jian
authors.initials: J
authors.lastname: Niu
authors.affiliation: General Surgery of the Hospital Affiliated Hospital of Xuzhou Medical University, Digestive Disease Research Laboratory of Xuzhou Medical University, Xuzhou, Jiangsu 221002, PR China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Wang
authors.affiliation: General Surgery of the Hospital Affiliated Hospital of Xuzhou Medical University, Digestive Disease Research Laboratory of Xuzhou Medical University, Xuzhou, Jiangsu 221002, PR China.
authors.forename: Ji
authors.initials: J
authors.lastname: Wang
authors.affiliation: General Surgery of the Hospital Affiliated Hospital of Xuzhou Medical University, Digestive Disease Research Laboratory of Xuzhou Medical University, Xuzhou, Jiangsu 221002, PR China.
authors.forename: Liu
authors.initials: L
authors.lastname: Bin
authors.affiliation: The University of Texas Graduate School of Biomedical Sciences at Houston, MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Hu
mesh_terms: D000818:Animals; D017209:Apoptosis; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage / Q000494:pharmacology*; D004334:Drug Administration Schedule; D056945:Hep G2 Cells; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D000072179:Interleukin-1 Receptor-Like 1 Protein / Q000378:metabolism*; D008113:Liver Neoplasms / Q000378:metabolism; D008114:Liver Neoplasms, Experimental; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D051379:Mice; D008819:Mice, Nude; D033581:Stem Cell Transplantation
chemical_list: C079241:IL1RL1 protein, human; D000072179:Interleukin-1 Receptor-Like 1 Protein; D004317:Doxorubicin
keywords: gene therapy; liver cancer; mesenchymal stem cells; soluble Fms-like tyrosine kinase-1 (sFlt1); vascular endothelial growth factor