Pancreatic tumor mass in a xenograft mouse model is decreased by treatment with therapeutic stem cells following introduction of therapeutic genes

Kim,Doo-Jin; Yi,Bo-Rim; Lee,Hye-Rim; Kim,Seung U.; Choi,Kyung-Chul

doi:10.3892/or.2013.2564

Pancreatic tumor mass in a xenograft mouse model is decreased by treatment with therapeutic stem cells following introduction of therapeutic genes

Authors:
- Doo-Jin Kim
- Bo-Rim Yi
- Hye-Rim Lee
- Seung U. Kim
- Kyung-Chul Choi
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Affiliations: Laboratory of Veterinary Biochemistry and Immunology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk, Republic of Korea, Medical Research Institute, Chung-Ang University College of Medicine, Seoul, Republic of Korea
Published online on: June 25, 2013 https://doi.org/10.3892/or.2013.2564
Pages: 1129-1136

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Abstract

Pancreatic cancer is the fourth most common cause of cancer-related mortality. In the present study, we employed 2 types of therapeutic stem cells expressing cytosine deaminase (CD) with or without human interferon-β (IFN‑β), HB1.F3.CD and HB1.F3.CD.IFN-β cells, respectively, to selectively treat pancreatic cancer. The CD gene converts the non-toxic prodrug, 5-flurorocytosine (5-FC), into the toxic agent, 5-fluorouracil (5-FU). In addition, human IFN-β is a potent cytokine that has antitumor effects. To generate a xenograft mouse model, PANC-1 cells (2x106/mouse) cultured in DMEM containing 10% FBS were mixed with Matrigel and were subcutaneously injected into Balb/c nu/nu mice. In the migration assay, the stem cells expressing the CD or IFN-β gene effectively migrated toward the pancreatic cancer cells, suggesting the presence of chemoattractant factors secreted by the pancreatic tumors. In the co-culture and MTT assay, antitumor activity of the therapeutic stem cells was observed in the presence of 5-FC was shown that the growth of PANC-1 cells was inhibited. Furthermore, these effects were confirmed in the xenograft mouse model bearing tumors originating from PANC-1 cells. Analyses by histological and fluorescence microscopy showed that treatment with the stem cells resulted in the inhibition of pancreatic cancer growth in the presence of 5-FC. Taken together, these results indicate that stem cells expressing the CD and/or IFN-β gene can be used to effectively treat pancreatic cancer and reduce the side-effects associated with conventional therapies.

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