OBJECTIVE To observe the effects of sense and antisense oligodeoxynucleotides of tankyrase 1 （TANK1-SODN and TANK1-ASODN） on murine tumor growth following intratumoral injection, investigate the actual suppressing r...OBJECTIVE To observe the effects of sense and antisense oligodeoxynucleotides of tankyrase 1 （TANK1-SODN and TANK1-ASODN） on murine tumor growth following intratumoral injection, investigate the actual suppressing result and mechanism of TANK1-ASODN on cancer cell proliferation, and discuss the possibility of using it in gene therapy on human lung cancer cells. METHODS After BALB/c nude mice had been subcutaneously inoculated with human lung cancer cell line CALU and it had grown into tumor nodules, we distributed these mice randomly into 3 groups： 4 in saline treatment group, and 5 each in TANK1-SODN group, and TANK1-ASODN groups. Then multiple direct intratumoral injections of synthesized TANK1-ASODN given continuously into tumor nodules for 16 days, this was compared with TANK1-SODN and saline control groups. During the experiment we measured the tumor volume every 5 days with vernier calipers; observed the histopathological characteristics of tumor tissues under microscope; went further to detect the minute changing of ultrastructure of cancer cells by electron microscope; tested the expression levels of ki67 and hTERT protein by means of SABC immunohistochemical method; and detected the lung cancer cells＇ hTERT mRNA expression level by hybridization in situ （ISH） in each group. RESULTS After 16 days of continuous injection, the tumor volume in TANK1-ASODN group was significantly smaller than the other 2 groups （both P 〈 0.01）; quite a lot of tumor cell degeneration and necrosis were observed in mice given TANK1-ASODN. The results of electron microscope also showed that TANK1-ASODN has the power to kill cancer cells in various ways. Moreover, statistically signi.cant decreases in the positive expression ratio of Ki67 Labeling Index （P 〈 0.01）, hTERT protein （P 〈 0.01）, and hTERT mRNA （P 〈 0.01） were consistently observed in the TANK1-ASODN group. CONCLUSION Human lung cancer cell line CALU expressed high telomerase activity. TANK1-ASODN had the ability to decline the high expression level of hTERT; inhibit the activity of telomerase, accelerate tumor cell degeneration and necrosis; and then suppress the proliferation of cancer cells.展开更多
线粒体自噬是一种清除受损或多余线粒体的过程,在调节细胞内线粒体质量和维持线粒体能量代谢等方面发挥重要作用。TANK结合激酶1(TANK-binding kinase 1,TBK1)是一种多功能的丝氨酸/苏氨酸蛋白激酶,同时参与调控PTEN诱导假定激酶1(PTEN-...线粒体自噬是一种清除受损或多余线粒体的过程,在调节细胞内线粒体质量和维持线粒体能量代谢等方面发挥重要作用。TANK结合激酶1(TANK-binding kinase 1,TBK1)是一种多功能的丝氨酸/苏氨酸蛋白激酶,同时参与调控PTEN诱导假定激酶1(PTEN-induced putative kinase 1,PINK1)/Parkin依赖性和非依赖性线粒体自噬过程。近期研究表明,TBK1可磷酸化视神经蛋白(optineurin,OPTN)、p62/sequestosome-1、Ras相关GTP结合蛋白7(Ras-related GTP binding protein 7,Rab7)等自噬相关蛋白,并介导核点蛋白52(nuclear dot protein 52,NDP52)与UNC-51样自噬激活激酶1(UNC-51 like autophagy activating kinase 1,ULK1)复合物相结合,以及TAX1结合蛋白1(TAX1-binding protein 1,TAX1BP1)与微管相关蛋白1轻链3(microtubule-associated protein 1 light chain 3,LC3)相结合,从而增强PINK1/Parkin依赖性线粒体自噬。TBK1亦可作为AMP活化蛋白激酶(AMP-activatedproteinkinase,AMPK)/ULK1自噬通路的作用底物而被激活,再通过磷酸化动力相关蛋白1(dynamin-related protein 1,Drp1)、Rab7促进PINK1/Parkin非依赖性线粒体自噬。本文对TBK1在PINK1/Parkin依赖性和非依赖性线粒体自噬中的作用及机制进行了综述。展开更多
Aiming to meet the demand of the country＇ s nuclear demonstration project on the CAP1400 nuclear power plant, Baosteel uses the roll-bonding technology and develops the SA-533 Type B CL. 1 ＋ SA-240 Type 304L high-st...Aiming to meet the demand of the country＇ s nuclear demonstration project on the CAP1400 nuclear power plant, Baosteel uses the roll-bonding technology and develops the SA-533 Type B CL. 1 ＋ SA-240 Type 304L high-strength and high-toughness clad steel plate with a shear strength of over 310 MPa for the nuclear power plant＇ s safety injection tank. The properties of the quenched and tempered and the simulated post-weld heat treatment states are systematically studied herein through a comprehensive inspection and evaluation of the composition,microstructure,and properties of the clad steel plate. The results show that the bonding interface has high shear strength and that the base metal has high strength and good toughness at low temperatures. Hence, the performance fully meets the technical requirements of the CAP1400 nuclear power plant＇ s safety injection tank in the country＇ s nuclear demonstration project. The roll-bonded clad steel plate can be used to manufacture the safety injection tank of the CAP1400 nuclear power plant.展开更多
文摘OBJECTIVE To observe the effects of sense and antisense oligodeoxynucleotides of tankyrase 1 （TANK1-SODN and TANK1-ASODN） on murine tumor growth following intratumoral injection, investigate the actual suppressing result and mechanism of TANK1-ASODN on cancer cell proliferation, and discuss the possibility of using it in gene therapy on human lung cancer cells. METHODS After BALB/c nude mice had been subcutaneously inoculated with human lung cancer cell line CALU and it had grown into tumor nodules, we distributed these mice randomly into 3 groups： 4 in saline treatment group, and 5 each in TANK1-SODN group, and TANK1-ASODN groups. Then multiple direct intratumoral injections of synthesized TANK1-ASODN given continuously into tumor nodules for 16 days, this was compared with TANK1-SODN and saline control groups. During the experiment we measured the tumor volume every 5 days with vernier calipers; observed the histopathological characteristics of tumor tissues under microscope; went further to detect the minute changing of ultrastructure of cancer cells by electron microscope; tested the expression levels of ki67 and hTERT protein by means of SABC immunohistochemical method; and detected the lung cancer cells＇ hTERT mRNA expression level by hybridization in situ （ISH） in each group. RESULTS After 16 days of continuous injection, the tumor volume in TANK1-ASODN group was significantly smaller than the other 2 groups （both P 〈 0.01）; quite a lot of tumor cell degeneration and necrosis were observed in mice given TANK1-ASODN. The results of electron microscope also showed that TANK1-ASODN has the power to kill cancer cells in various ways. Moreover, statistically signi.cant decreases in the positive expression ratio of Ki67 Labeling Index （P 〈 0.01）, hTERT protein （P 〈 0.01）, and hTERT mRNA （P 〈 0.01） were consistently observed in the TANK1-ASODN group. CONCLUSION Human lung cancer cell line CALU expressed high telomerase activity. TANK1-ASODN had the ability to decline the high expression level of hTERT; inhibit the activity of telomerase, accelerate tumor cell degeneration and necrosis; and then suppress the proliferation of cancer cells.
基金supported by the National Natural Science Foundation of China(No.31900842,31960192)the Natural Science Foundation of Sichuan Province,China(No.2023NSFSC1524)+3 种基金Jiangxi Provincial Science Fund for Distinguished Young Scholars(No.20202ACBL216004)Zhejiang Provincial Natural Science Foundation(No.LY23C110001)Basic Scientific Research Project of Wenzhou(No.Y20220209)Innovative Project of Institute of Sports Medicine and Health of Chengdu Sport University(No.CX21A01)。
文摘线粒体自噬是一种清除受损或多余线粒体的过程,在调节细胞内线粒体质量和维持线粒体能量代谢等方面发挥重要作用。TANK结合激酶1(TANK-binding kinase 1,TBK1)是一种多功能的丝氨酸/苏氨酸蛋白激酶,同时参与调控PTEN诱导假定激酶1(PTEN-induced putative kinase 1,PINK1)/Parkin依赖性和非依赖性线粒体自噬过程。近期研究表明,TBK1可磷酸化视神经蛋白(optineurin,OPTN)、p62/sequestosome-1、Ras相关GTP结合蛋白7(Ras-related GTP binding protein 7,Rab7)等自噬相关蛋白,并介导核点蛋白52(nuclear dot protein 52,NDP52)与UNC-51样自噬激活激酶1(UNC-51 like autophagy activating kinase 1,ULK1)复合物相结合,以及TAX1结合蛋白1(TAX1-binding protein 1,TAX1BP1)与微管相关蛋白1轻链3(microtubule-associated protein 1 light chain 3,LC3)相结合,从而增强PINK1/Parkin依赖性线粒体自噬。TBK1亦可作为AMP活化蛋白激酶(AMP-activatedproteinkinase,AMPK)/ULK1自噬通路的作用底物而被激活,再通过磷酸化动力相关蛋白1(dynamin-related protein 1,Drp1)、Rab7促进PINK1/Parkin非依赖性线粒体自噬。本文对TBK1在PINK1/Parkin依赖性和非依赖性线粒体自噬中的作用及机制进行了综述。
文摘Aiming to meet the demand of the country＇ s nuclear demonstration project on the CAP1400 nuclear power plant, Baosteel uses the roll-bonding technology and develops the SA-533 Type B CL. 1 ＋ SA-240 Type 304L high-strength and high-toughness clad steel plate with a shear strength of over 310 MPa for the nuclear power plant＇ s safety injection tank. The properties of the quenched and tempered and the simulated post-weld heat treatment states are systematically studied herein through a comprehensive inspection and evaluation of the composition,microstructure,and properties of the clad steel plate. The results show that the bonding interface has high shear strength and that the base metal has high strength and good toughness at low temperatures. Hence, the performance fully meets the technical requirements of the CAP1400 nuclear power plant＇ s safety injection tank in the country＇ s nuclear demonstration project. The roll-bonded clad steel plate can be used to manufacture the safety injection tank of the CAP1400 nuclear power plant.
