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The Study of Mesenchymal Stem Cell-TRAIL Complex Promotes Apoptosis of Pancreatic Cancer Cells

Author: JiangWei
Tutor: LuCaiDe
School: Ningbo University
Course: Surgery
Keywords: MSC TRAIL Pancreatic cancer apoptosis
CLC: R735.9
Type: Master's thesis
Year: 2013
Downloads: 1
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Abstract

Background and Objective: Pancreatic cancer, a highly malignant solid tumors, whichprognosis was poor, and the onset age was getting younger. Current clinical treatment of pancreaticcancer mainly depends on the surgical resection, but due to the concealment of pancreatic cancer,local diffusion easily and metastasis early. When in the clinic, most patients are already in the end-stage and lost the opportunity of surgical resection. Chemotherapy and radiation treatment ofpancreatic cancer have poor efficacy, the main reason is that the current treatment is lack of tumor-specific targeted measures. Mesenchymal stem cells (MSC) is a kind of adult pluripotent stem cellswhich can be able to differentiate into a variety of cells. Recent researches have found that theMSC not only has the self-renewal and multi-directional differentiation function, but also has thecharacteristics of directional migration and settlement. This feature makes the MSC can be settledin the tumor tissue, either the primary tumor or metastases, even small lesions which can not befound in conventional detection methods. TRAIL (TNF-related apoptosis-inducing ligand) wasfound in the third following TNF, FasL apoptotic molecules of the TNF family. TRAIL binds to itsreceptor can start the intracellular signal transduction, which can induce the apoptosis of a varietyof tumor cell lines in vitro, whereas the normal cell is insensitive. Five different TRAIL receptorshave been identified, including death receptors DR4and DR5that mediated apoptosis signaltransduction, and three decoy receptors: DcR1, DcR2and OPG, which impeded apoptosis signaltransduction, thereby inhibiting TRAIL-mediated apoptosis. This study was designed to constructMSC, an anti-tumor gene complex containing TRAIL,.and then co-cultured with tumor cells, andthen observe the ability to tumor cell apoptosis. So as to provide an experimental basis for thetreatment of pancreatic cancer using cells-gene dual targeted therapies.Methods: Isolated and purified the MSC from healthy voluteers’ bone marrow biopsies, andthen started revelent identification through primary culture, Using TRANS IT2020brought fromMIRUS company transfect the plasmid with TRAIL into the MSC conforming MSC-TRAILcomplex, and verified the effect of transfection by PCR.After conventional culture, determined theDR4and DR5receptor expression by flow cytometry. Mesenchymal stem cell-TRAIL complexco-cultured with pancreatic cancer cells to determine the MSC cell migration rate and induce theapoptosis of pancreatic cancer cell.Results:(1) MSC surface marker and directional differentiation was used by flow cytometryto confirm that the cell is MSC;(2) Determined the transfection expression of TRAIL by PCR; (3)Pancreatic cancer cell lines have DR4/DR5receptor expression by flow cytometry;(4) MSChas the ability to migrate to pancreatic cancer cell, MSC-TRAIL complex co-culture withpancreatic cancer cell lines in vitro can promote the apoptosis of pancreatic cancer cells.Conclusion: MSC has the ability to migrate to pancreatic cancer cell, MSC-TRAILcomplexes co-culture with pancreatic cancer cell lines in vitro can promote the apoptosis ofpancreatic cancer cells.

The Study of Mesenchymal Stem Cell-TRAIL Complex Promotes Apoptosis of Pancreatic Cancer Cells

Abstract

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