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      The Effect of HIF-1α siRNA on Growth and Chemosensitivity of Mia-paca Cell Line

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      https://www.riss.kr/link?id=A101617035

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      다국어 초록 (Multilingual Abstract) kakao i 다국어 번역

      Purpose: Hypoxia-inducible factor-1α (HIF-1α) primarily mediates the hypoxic response. HIF-1α induction by various stimuli contributes to cell proliferation and survival. To investigate the effect of HIF-1α, we used small interfering RNA (siRNA), and expected that cell apoptosis and sensitivity to chemotherapeutic drug increase, when we blocked the HIF-1α gene. Thus we performed in vitro and in vivo experiment to clarify the effect of hypoxia-inducible factor-1α on tumor growth. Received June 27, 2007
      Accepted October 9, 2007
      This paper was presented at the 9th World Congress on Gastrointestinal Cancer (WCGC) at Barcelona, Spain. (Jun 27-30, 2007).
      The corresponding author wishes to acknowledge the financial support of the Catholic Medical Center Research Foundation made in the program year of 2007 and the Sanofi-aventis.
      Reprint address: requests to Dr. Won Kyung Kang, Department of Surgery, The Catholic University of Korea, 505 Banpo-4, Seocho, Seoul 137-701, Korea. Tel: 82-2-590-2731, Fax: 82-2-590-1406, E-mail: wonkkang@catholic.ac.krMaterials and Methods: We made control and HIF-1α siRNA using vector plasmid and then transfected Mia-paca cell lines with these RNAs. After selection with geneticin, two new cell lines were made, confirmed via immunoblotting. After treating with gemcitabine, each cell line was assayed to confirm the effect of HIF-1α siRNA using the cell proliferation assay and capase-3 assay. And then in vivo study was performed using female athymic nude mice. After subcutaneously injecting each new cell lines, intraperitoneal gemicitabine chemotherapy was performed for 3 weeks. During that period, we analyzed the difference of tumor growth rate. Results: The tumor growth of HIF-1α siRNA-transfected group was slower than that of the control group both in vitro and in vivo experiment. Conclusion: The suppression of HIF-1α results in decrease of cell proliferation and increase of chemosensitivity of pancreatic cancer cell line. Therefore, targeting the HIF-1α may be useful treatment modality for some pancreatic cancers.
      번역하기

      Purpose: Hypoxia-inducible factor-1α (HIF-1α) primarily mediates the hypoxic response. HIF-1α induction by various stimuli contributes to cell proliferation and survival. To investigate the effect of HIF-1α, we used small interfering RNA (siRNA), ...

      Purpose: Hypoxia-inducible factor-1α (HIF-1α) primarily mediates the hypoxic response. HIF-1α induction by various stimuli contributes to cell proliferation and survival. To investigate the effect of HIF-1α, we used small interfering RNA (siRNA), and expected that cell apoptosis and sensitivity to chemotherapeutic drug increase, when we blocked the HIF-1α gene. Thus we performed in vitro and in vivo experiment to clarify the effect of hypoxia-inducible factor-1α on tumor growth. Received June 27, 2007
      Accepted October 9, 2007
      This paper was presented at the 9th World Congress on Gastrointestinal Cancer (WCGC) at Barcelona, Spain. (Jun 27-30, 2007).
      The corresponding author wishes to acknowledge the financial support of the Catholic Medical Center Research Foundation made in the program year of 2007 and the Sanofi-aventis.
      Reprint address: requests to Dr. Won Kyung Kang, Department of Surgery, The Catholic University of Korea, 505 Banpo-4, Seocho, Seoul 137-701, Korea. Tel: 82-2-590-2731, Fax: 82-2-590-1406, E-mail: wonkkang@catholic.ac.krMaterials and Methods: We made control and HIF-1α siRNA using vector plasmid and then transfected Mia-paca cell lines with these RNAs. After selection with geneticin, two new cell lines were made, confirmed via immunoblotting. After treating with gemcitabine, each cell line was assayed to confirm the effect of HIF-1α siRNA using the cell proliferation assay and capase-3 assay. And then in vivo study was performed using female athymic nude mice. After subcutaneously injecting each new cell lines, intraperitoneal gemicitabine chemotherapy was performed for 3 weeks. During that period, we analyzed the difference of tumor growth rate. Results: The tumor growth of HIF-1α siRNA-transfected group was slower than that of the control group both in vitro and in vivo experiment. Conclusion: The suppression of HIF-1α results in decrease of cell proliferation and increase of chemosensitivity of pancreatic cancer cell line. Therefore, targeting the HIF-1α may be useful treatment modality for some pancreatic cancers.

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      다국어 초록 (Multilingual Abstract) kakao i 다국어 번역

      Purpose: Hypoxia-inducible factor-1α (HIF-1α) primarily mediates the hypoxic response. HIF-1α induction by various stimuli contributes to cell proliferation and survival. To investigate the effect of HIF-1α, we used small interfering RNA (siRNA), and expected that cell apoptosis and sensitivity to chemotherapeutic drug increase, when we blocked the HIF-1α gene. Thus we performed in vitro and in vivo experiment to clarify the effect of hypoxia-inducible factor-1α on tumor growth. Received June 27, 2007
      Accepted October 9, 2007
      This paper was presented at the 9th World Congress on Gastrointestinal Cancer (WCGC) at Barcelona, Spain. (Jun 27-30, 2007).
      The corresponding author wishes to acknowledge the financial support of the Catholic Medical Center Research Foundation made in the program year of 2007 and the Sanofi-aventis.
      Reprint address: requests to Dr. Won Kyung Kang, Department of Surgery, The Catholic University of Korea, 505 Banpo-4, Seocho, Seoul 137-701, Korea. Tel: 82-2-590-2731, Fax: 82-2-590-1406, E-mail: wonkkang@catholic.ac.krMaterials and Methods: We made control and HIF-1α siRNA using vector plasmid and then transfected Mia-paca cell lines with these RNAs. After selection with geneticin, two new cell lines were made, confirmed via immunoblotting. After treating with gemcitabine, each cell line was assayed to confirm the effect of HIF-1α siRNA using the cell proliferation assay and capase-3 assay. And then in vivo study was performed using female athymic nude mice. After subcutaneously injecting each new cell lines, intraperitoneal gemicitabine chemotherapy was performed for 3 weeks. During that period, we analyzed the difference of tumor growth rate. Results: The tumor growth of HIF-1α siRNA-transfected group was slower than that of the control group both in vitro and in vivo experiment. Conclusion: The suppression of HIF-1α results in decrease of cell proliferation and increase of chemosensitivity of pancreatic cancer cell line. Therefore, targeting the HIF-1α may be useful treatment modality for some pancreatic cancers.
      번역하기

      Purpose: Hypoxia-inducible factor-1α (HIF-1α) primarily mediates the hypoxic response. HIF-1α induction by various stimuli contributes to cell proliferation and survival. To investigate the effect of HIF-1α, we used small interfering RNA (siRNA), ...

      Purpose: Hypoxia-inducible factor-1α (HIF-1α) primarily mediates the hypoxic response. HIF-1α induction by various stimuli contributes to cell proliferation and survival. To investigate the effect of HIF-1α, we used small interfering RNA (siRNA), and expected that cell apoptosis and sensitivity to chemotherapeutic drug increase, when we blocked the HIF-1α gene. Thus we performed in vitro and in vivo experiment to clarify the effect of hypoxia-inducible factor-1α on tumor growth. Received June 27, 2007
      Accepted October 9, 2007
      This paper was presented at the 9th World Congress on Gastrointestinal Cancer (WCGC) at Barcelona, Spain. (Jun 27-30, 2007).
      The corresponding author wishes to acknowledge the financial support of the Catholic Medical Center Research Foundation made in the program year of 2007 and the Sanofi-aventis.
      Reprint address: requests to Dr. Won Kyung Kang, Department of Surgery, The Catholic University of Korea, 505 Banpo-4, Seocho, Seoul 137-701, Korea. Tel: 82-2-590-2731, Fax: 82-2-590-1406, E-mail: wonkkang@catholic.ac.krMaterials and Methods: We made control and HIF-1α siRNA using vector plasmid and then transfected Mia-paca cell lines with these RNAs. After selection with geneticin, two new cell lines were made, confirmed via immunoblotting. After treating with gemcitabine, each cell line was assayed to confirm the effect of HIF-1α siRNA using the cell proliferation assay and capase-3 assay. And then in vivo study was performed using female athymic nude mice. After subcutaneously injecting each new cell lines, intraperitoneal gemicitabine chemotherapy was performed for 3 weeks. During that period, we analyzed the difference of tumor growth rate. Results: The tumor growth of HIF-1α siRNA-transfected group was slower than that of the control group both in vitro and in vivo experiment. Conclusion: The suppression of HIF-1α results in decrease of cell proliferation and increase of chemosensitivity of pancreatic cancer cell line. Therefore, targeting the HIF-1α may be useful treatment modality for some pancreatic cancers.

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      참고문헌 (Reference)

      1 Karagiannis TC, "siRNAs: mechanism of RNA interference, in vivo and potential clinical applications" 3 : 1069-1074, 2004

      2 Dorsett Y, "siRNAs: applications in functional genomics and potential as therapeutics" 3 : 318-329, 2004

      3 Chang HS, "Using siRNA technique to generate transgenic animals with spatiotemporal and conditional gene knockdown" 165 : 1535-1541, 2004

      4 Yang L, "Tumor-specific gene expression using the survivin promoter is further increased by hypoxia" 11 : 1215-1223, 2440

      5 Cantley LC, "The phosphoinositide 3-kinase pathway" 296 : 1655-1657, 2002

      6 Bae SH, "Sumoylation increases HIF-1alpha stability and its transcriptional activity" 324 : 394-400, 2004

      7 Fujiwara S, "Silencing hypoxia- inducible factor-1alpha inhibits cell migration and invasion under hypoxic environment in malignant gliomas" 30 : 793-802, 2007

      8 Ryther RC, "Phillips JA 3rd, Patton JG. siRNA therapeutics: big potential from small RNAs" 12 : 5-11, 2005

      9 Déry MA, "Hypoxia- inducible factor 1: regulation by hypoxic and non- hypoxic activators" 37 : 353-340, 2005

      10 Zagórska A, "HIF-1: the knowns and unknowns of hypoxia sensing" 51 : 563-585, 2004

      1 Karagiannis TC, "siRNAs: mechanism of RNA interference, in vivo and potential clinical applications" 3 : 1069-1074, 2004

      2 Dorsett Y, "siRNAs: applications in functional genomics and potential as therapeutics" 3 : 318-329, 2004

      3 Chang HS, "Using siRNA technique to generate transgenic animals with spatiotemporal and conditional gene knockdown" 165 : 1535-1541, 2004

      4 Yang L, "Tumor-specific gene expression using the survivin promoter is further increased by hypoxia" 11 : 1215-1223, 2440

      5 Cantley LC, "The phosphoinositide 3-kinase pathway" 296 : 1655-1657, 2002

      6 Bae SH, "Sumoylation increases HIF-1alpha stability and its transcriptional activity" 324 : 394-400, 2004

      7 Fujiwara S, "Silencing hypoxia- inducible factor-1alpha inhibits cell migration and invasion under hypoxic environment in malignant gliomas" 30 : 793-802, 2007

      8 Ryther RC, "Phillips JA 3rd, Patton JG. siRNA therapeutics: big potential from small RNAs" 12 : 5-11, 2005

      9 Déry MA, "Hypoxia- inducible factor 1: regulation by hypoxic and non- hypoxic activators" 37 : 353-340, 2005

      10 Zagórska A, "HIF-1: the knowns and unknowns of hypoxia sensing" 51 : 563-585, 2004

      11 Bold RJ, "Gemcitabine-induced programmed cell death (apoptosis) of human pancreatic carcinoma is determined by Bcl-2 content" 6 : 279-285, 1999

      12 Zhao Q, "Effects of YC-1 on hypoxia-inducible factor 1-driven transcription activity, cell proliferative vitality, and apoptosis in hypoxic human pancreatic cancer cells" 34 : 242-247, 2007

      13 Jemal A, "Cancer statistics" 57 : 43-66, 2007

      14 Debatin KM, "Apoptosis pathways in cancer and cancer therapy" 53 : 153-159, 2004

      15 Hsieh AC, "A library of siRNA duplexes targeting the phosphoinositide 3-kinase pathway: determinants of gene silencing for use in cell-based screens" 32 : 893-901, 2004

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