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Author(s): Leilei Liang, Fuping Guan, Yinlin Ge
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DOI: 10.18483/ijSci.1591
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Volume 7 - Mar 2018
Abstract
Objective: To explore the role of PD-1 expression level on the growth of hepatocarcinoma line H22. Methods: Tumor-bearing mice model was established with H22 cells in ICR mice. The model mice were randomly divided into two groups, control group and PD-1 interference group (PD-1-siRNA). The control group was injected transfection reagent, wherase the PD-1-siRNA was given the transfection reagent with PD-1-siRNA. Observed the life condition and tumor growth of mice, measured and recorded the tumor volume. The mRNA expression levels of PD-L1, PD-L2, P53, caspase-3 and IL-6 in tumor tissue were detected by real time fluorescence quantitative PCR (qPCR) technique. The expression of IFN-γ cytokines in spleen and tumor tissue was detected by ELISA. The ratio of Bax and Bcl-2 protein was detected by Western Blot to analyze the effect of PD-1-siRNA on tumor cell apoptosis. Results: Compared with control group, mice of PD-1-siRNA in better quality of life, survival time prolonged and the tumor volume of mouse was significantly reduced. The mRNA expression levels of PD-L1, PD-L2, P53 and caspase-3 were increased, others, IL-6 expression level was significantly decreased. The expression level of IFN-γ was up-regulated in spleen and tumor tissues. Western blot shown that the ratio of Bax and Bcl-2 was significantly increased. Conclusion: Interfere of PD-1 expression can effectively inhibit the growth of hepatocarcinoma cell H22 in mice.
Keywords
PD-1-siPD-1, PD-L1, Immunotherapy, H22 hepatoma cells, IFN-γ
References
- Jemal A, Bray F, Center M M, et al. Global cancer statistics. CA. Cancer J Clin[J]. Ca A Cancer Journal for Clinicians, 2011, 61(2): 69-90.
- Ansell S M, Lesokhin A M, Borrello I, et al. PD-1 Blockade with Nivolumab in Relapsed or Refractory Hodgkin's Lymphoma[J]. The New England journal of medicine, 2015, 372(4): 311-319.
- Swaika A, Hammond W A, Joseph R W. Current state of anti-PD-L1 and anti-PD-1 agents in cancer therapy[J]. Molecular Immunology, 2015, 67(2, Part A): 4-17.
- Kim J M, Chen D S. Immune escape to PD-L1/PD-1 blockade: seven steps to success (or failure)[J]. Annals of Oncology, 2016, 27(8): 1492-1504.
- Patsoukis N, Brown J, Petkova V, et al. Selective Effects of PD-1 on Akt and Ras Pathways Regulate Molecular Components of the Cell Cycle and Inhibit T Cell Proliferation[J]. Science signaling, 2012, 5(230): ra46-ra46.
- Ma W, Gilligan B M, Yuan J, et al. Current status and perspectives in translational biomarker research for PD-1/PD-L1 immune checkpoint blockade therapy[J]. Journal of Hematology & Oncology, 2016, 9: 47.
- Chauvin J-M, Pagliano O, Fourcade J, et al. TIGIT and PD-1 impair tumor antigen–specific CD8(+) T cells in melanoma patients[J]. The Journal of Clinical Investigation, 2015, 125(5): 2046-2058.
- Smyth M J, Ngiow S F, Ribas A, et al. Combination cancer immunotherapies tailored to the tumour microenvironment[J]. Nature Reviews Clinical Oncology, 2015, 13: 143.
- Buchbinder E I, Desai A. CTLA-4 and PD-1 Pathways: Similarities, Differences, and Implications of Their Inhibition[J]. American Journal of Clinical Oncology, 2016, 39(1): 98-106.
- Reck M, Rodríguez-Abreu D, Robinson A G, et al. Pembrolizumab versus Chemotherapy for PD-L1–Positive Non–Small-Cell Lung Cancer[J]. New England Journal of Medicine, 2016, 375(19): 1823-1833.
- Meng X, Huang Z, Teng F, et al. Predictive biomarkers in PD-1/PD-L1 checkpoint blockade immunotherapy[J]. Cancer Treatment Reviews, 2015, 41(10): 868-876.
- Eyre T A, Collins G P. Immune checkpoint inhibition in lymphoid disease[J]. British Journal of Haematology, 2015, 170(3): 291-304.
- Shih K-S, Lin C-C, Hung H-F, et al. One-Step Chromatographic Purification of Helicobacter pylori Neutrophil-Activating Protein Expressed in Bacillus subtilis[J]. PLoS ONE, 2013, 8(4): e60786.
- Rusolo F, Pucci B, Colonna G, et al. Evaluation of Selenite Effects on Selenoproteins and Cytokinome in Human Hepatoma Cell Lines[J]. Molecules, 2013, 18(3): 2549.
- Park H J, Kusnadi A, Lee E-J, et al. Tumor-infiltrating regulatory T cells delineated by upregulation of PD-1 and inhibitory receptors[J]. Cellular Immunology, 2012, 278(1): 76-83.
- Jansson M D, Damas N D, Lees M, et al. miR-339-5p regulates the p53 tumor-suppressor pathway by targeting MDM2[J]. Oncogene, 2014, 34: 1908.
- Ramani P, Nash R, Rogers C A. Aurora kinase A is superior to Ki67 as a prognostic indicator of survival in neuroblastoma[J]. Histopathology, 2015, 66(3): 370-379.
- Fuchs E J, Mckenna K A, Bedi A. p53-dependent DNA Damage-induced Apoptosis Requires Fas/APO-1-independent Activation of CPP32β[J]. Cancer Research, 1997, 57(13): 2550-2554.
- Khalil H, Bertrand M J M, Vandenabeele P, et al. Caspase-3 and RasGAP: a stress-sensing survival/demise switch[J]. Trends in Cell Biology, 2014, 24(2): 83-89.
- Steller H. Mechanisms and genes of cellular suicide[J]. Science, 1995, 267(5203): 1445-1449.
- Tagliamonte M, Petrizzo A, Tornesello M L, et al. Combinatorial immunotherapy strategies for hepatocellular carcinoma[J]. Current Opinion in Immunology, 2016, 39: 103-113.
- Mikhail S, Cosgrove D, Zeidan A. Hepatocellular carcinoma: systemic therapies and future perspectives[J]. Expert Review of Anticancer Therapy, 2014, 14(10): 1205-1218.
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