Inhibitory effect of genetically engineered mesenchymal stem cells with Apoptin on hepatoma cells in vitro and in vivo
- 374 Downloads
Hepatocellular carcinoma (HCC) is an aggressive tumor and has become one of the most frequent causes of cancer death in the world. The rate of post-operative recurrence and metastasis are still high even though after surgical resection. It is a difficult problem with extraordinary importance for the clinical treatment. So stem cell therapy becomes one of the anti-tumor biotherapy methods which is exploring. Due to the feature of homing to tumor site and immunosuppressive, mesenchymal stem cells (MSCs) have the capacity of gene treatment to tumor as a vehicle. Apoptin derived from chicken anemia virus is one kind of protein with an inherent ability to lyse cancer cells while leaving normal cells unharmed. Adenovirus (Ad) vectors can be modified to deliver therapeutic genes with the advantages of low toxicity and high transfer capacity. Now it has not been reported that combining MSCs and Adenovirus with Apoptin are used in HCC treatment. This study intends to construct recombinant adenovirus which expresses Apoptin and then infects human bone marrow MSCs, and explore the migration of MSCs to the hepatoma cells and inhibitory effect of genetically engineered mesenchymal stem cells with Apoptin on hepatoma cells in vitro and in vivo. Our research successfully established the recombinant Ad which was constructed by Ad system, and obtained MSCs which could secrete Apoptin. We found that both the modified MSCs with Apoptin and their conditional medium significantly inhibited the proliferation of liver cancer cells HepG2, which provided a novel means and experimental basis for stem cell treatment for HCC. This study tries to search for a stem cell therapy for cancers, which will provide a new approach and experimental basis for the clinical treatment of cancer. At the same time, this research will also provide experimental basis for a novel in vivo drug delivery system through stem cells as vehicle, which will resolve immune rejection induced by repeated applications of drug directly delivered by Ad vectors and reduce the high cost of a large-scale production and purification of exogenous drugs.
KeywordsHepatocellular carcinoma Mesenchymal stem cells Apoptin Inhibitory
This study was supported by the National Natural Science Foundation of China (81201762) and the National High Technology Research and Development Program of China (2015YJS164).
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted.
- 3.Theise ND, Chen CJ, Kew MC (2014) Liver cancer. World Cancer Report, pp 577–593Google Scholar
- 17.Maddika S, Booy EP, Johar D, Gibson SB, Ghavami S, Los M (2005) Cancer-specific toxicity of Apoptin is independent of death receptors but involves the loss of mitochondrial membrane potential and the release of mitochondrial cell-death mediators by a Nur7-dependent pathway. J Cell Sci 118(19):4485–4493CrossRefPubMedGoogle Scholar