Li Zhang1,2, Yi Wei3, Xiaowei Yan4, Na Li1, Haolan Song5, Li Yang6, Yang Wu6, Yu-Feng Xi6, Hua-Wei Weng1, Jian-Hua Li1, Edward H Lin7, Li-Qun Zou1,6. 1. Department of Medical Oncology, Cancer Center, West China Hospital of Sichuan University, Chengdu 610041, China. 2. National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen 518116, China. 3. The Centre Transport Department of West China Hospital, Sichuan University, Chengdu 610065, China. 4. Institute for Systems Biology, Seattle, Washington, USA. 5. Department of Laboratory Medicine, West China Hospital of Sichuan University, Chengdu 610041, China. 6. State Key Laboratory of Biotherapy, Sichuan University, Chengdu 610065, China. 7. P4 Medicine Institute, University of Washington, Seattle, Washington, USA.
Abstract
BACKGROUND: The relationship between survivin and extranodal, nasal-type natural killer/T cell lymphoma (ENKTCL) was unclearly established yet. We here studied the potential prognostic roles of survivin and its implication as a target in ENKTCL therapy. METHODS: ENKTCL patients' peripheral blood were collected and tested by ELISA. ENKTCL cell lines were cultured with or without survivin inhibitor and tested by MTT and Flow cytometry. According to the gene expression profiles from the ArrayExpress Archive under E-TABM-702, survivin co-regulated cluster was established by Coupled Two-way Clustering Algorithm. RESULTS: Seventeen point six percent of total 17 ENKTCL patients were serum survivin-positive. These patients had poorer outcome than that of negative cases (P<0.01). Analysis of survivin co-regulation genes in ENKTCL revealed that survivin was significantly involved in pluripotency, drug resistance, cell cycle and proliferation, indicating that it should be one of key regulators in ENKTCL and might be a latent therapeutic target. Our results just showed that YM155, a survivin inhibitor, had strong anti-tumor effect on ENKTCL cell lines in a dose dependent manner. It increased sub-G1 phase population and reduced G1- and G2-M phase populations (P<0.05). In addition, combining YM155 with DDP induced a larger decrease in cell viability than either agent alone and had a higher inhibition rate than Bliss index, suggesting their synergistic inhibition. CONCLUSIONS: We concluded that survivin was a potential prognostic marker and a critical regulatory molecule in the pathological process of ENKTCL. It would be a promising target in drugs discovery for ENKTCL therapy.
BACKGROUND: The relationship between survivin and extranodal, nasal-type natural killer/T cell lymphoma (ENKTCL) was unclearly established yet. We here studied the potential prognostic roles of survivin and its implication as a target in ENKTCL therapy. METHODS: ENKTCL patients' peripheral blood were collected and tested by ELISA. ENKTCL cell lines were cultured with or without survivin inhibitor and tested by MTT and Flow cytometry. According to the gene expression profiles from the ArrayExpress Archive under E-TABM-702, survivin co-regulated cluster was established by Coupled Two-way Clustering Algorithm. RESULTS: Seventeen point six percent of total 17 ENKTCL patients were serum survivin-positive. These patients had poorer outcome than that of negative cases (P<0.01). Analysis of survivin co-regulation genes in ENKTCL revealed that survivin was significantly involved in pluripotency, drug resistance, cell cycle and proliferation, indicating that it should be one of key regulators in ENKTCL and might be a latent therapeutic target. Our results just showed that YM155, a survivin inhibitor, had strong anti-tumor effect on ENKTCL cell lines in a dose dependent manner. It increased sub-G1 phase population and reduced G1- and G2-M phase populations (P<0.05). In addition, combining YM155 with DDP induced a larger decrease in cell viability than either agent alone and had a higher inhibition rate than Bliss index, suggesting their synergistic inhibition. CONCLUSIONS: We concluded that survivin was a potential prognostic marker and a critical regulatory molecule in the pathological process of ENKTCL. It would be a promising target in drugs discovery for ENKTCL therapy.
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