Combination Doxorubicin and Interferon-α Therapy Stimulates Immunogenicity of Murine Pancreatic Cancer Panc02 Cells via Up-regulation of NKG2D ligands and MHC Class I

Wang, Wen-Jia; Qin, Si-Hao; Zhang, Ji-Wei; Jiang, Yue-Yao; Zhang, Jin-Nan; Zhao, Lei

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자료유형: 학술저널

저자정보: Wang, Wen-Jia (Institute of Pharmacy, Tumor Hospital of Jilin Province) Qin, Si-Hao (Institute of Medicine, Tumor Hospital of Jilin Province) Zhang, Ji-Wei (Department of Neurosurgery, Tumor Hospital of Jilin Province) Jiang, Yue-Yao (Institute of Pharmacy, Tumor Hospital of Jilin Province) Zhang, Jin-Nan (Department of Neurosurgery, China-Japan Friendship Hospital) Zhao, Lei (Institute of Frontier Medical Science, Jilin University)

저널정보: 아시아태평양암예방학회 Asian Pacific journal of cancer prevention : APJCP Asian Pacific journal of cancer prevention : APJCP 제15권 제22호

발행연도: 2014.1

수록면: 9,667 - 9,672 (6page)

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Background: Pancreatic adenocarcinoma is a malignant gastrointestinal cancer with significant morbidity and mortality. Despite severe side effects of chemotherapy, the use of immunotherapy combined with chemotherapy has emerged as a common clinical treatment. In this study, we investigated the efficacy of the combined doxorubicin and interferon-${\alpha}$ (IFN-${\alpha}$) therapy on murine pancreatic cancer Panc02 cells in vitro and in vivo and underlying mechanisms. Materials and Methods: A Panc02-bearing mouse model was established to determine whether doxorubicin and interferon-${\alpha}$ (IFN-${\alpha}$) could effectively inhibit tumor growth in vivo. Cytotoxicity of natural killer (NK) cells and cytotoxic T lymphocytes (CTLs) was evaluated using a standard LDH release assay. To evaluate the relevance of NK cells and CD8 T cells to the combination therapy-mediated anti-tumor effects, they were depleted in tumor-bearing mice by injecting anti-asialo-GM-1 antibodies or anti-CD8 antibodies, respectively. Finally, the influence of doxorubicin+interferon-${\alpha}$ (IFN-${\alpha}$) on the ligands of NK and T cells was assessed by flow cytometry. Results: The combination therapy group demonstrated a significant inhibition of growth of Panc02 in vivo, resulting from activated cytotoxicity of NK cells and CTLs. Depleting CD8 T cells or NK cells reduced the anticancer effects mediated by immunochemotherapy. Furthermore, the doxorubicin+IFN-a treatment increased the expression of major histocompatibility complex class I (MHC I) and NKG2D ligands on Panc02 cells, suggesting that the combined therapy may be a potential strategy for enhancing immunogenicity of tumors. All these data indicate that the combination therapy using doxorubicin and interferon-${\alpha}$ (IFN-${\alpha}$) may be a potential strategy for treating pancreatic adenocarcinoma.

#Pancreatic cancer #interferon- ${alpha}$ #doxorubicin #combination therapy

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