Research Paper Volume 8, Issue 12 pp 3520—3534
Delivery of sFIT-1 engineered MSCs in combination with a continuous low-dose doxorubicin treatment prevents growth of liver cancer
- 1 General Surgery of the Hospital Affiliated Hospital of Xuzhou Medical University, Digestive Disease Research Laboratory of Xuzhou Medical University, Xuzhou, Jiangsu 221002, PR China
- 2 The University of Texas Graduate School of Biomedical Sciences at Houston, MD Anderson Cancer Center, Houston, TX 77030, USA
Received: November 7, 2016 Accepted: December 12, 2016 Published: December 28, 2016
https://doi.org/10.18632/aging.101146How to Cite
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.
Abbreviations
BCA: Bicinchoninic acid; FBS: Fetal bovine serum; PBS: Phosphate buffered saline; PVDF: Polyvinylidene difluoride; HE: Hematoxylin and eosin; MTT 3: 4,5- dimethylthiazol‐2yl)‐2,5-diphenyltetrazoliumbromide; VEGF: Vascular endothelial growth factor; Flk-1 /KDR: fetal liver kinase-1/kinase insert domain containing receptor; MSCs: Mesenchymal stem cells; HUVEC: human umbilical vein endothelial cells; Zvad: carbobenzoxy-valyl-alanyl-aspartyl-[O-methyl]-fluoromethylketone; PCNA: nuclear proliferating cell nuclear antigen; MVD: microvessels density; CM: concentrated conditioned medium; sFlt1: soluble Fms-like tyrosine kinase-1.