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豹蛙酶的抗肿瘤作用研究进展 被引量:1

Review of the anti-tumor role of onconase
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摘要 豹蛙酶(onconase)又称抗瘤酶、P30蛋白等,属核糖核酸酶A超家族成员。豹蛙酶是目前唯一用于临床试验阶段的核糖核酸酶,它的核糖核酸酶活性低,细胞毒性较强,对体内外多种肿瘤有很强的杀伤作用,是当前全球重点研究的100种新药之一。豹蛙酶在北极蛙的早期胚胎中被首次发现,它主要通过破坏RNA从而抑制蛋白质合成,诱导肿瘤细胞凋亡,此外还有其他抗肿瘤机制,如影响特定基因的表达和破坏端粒酶RNA。豹蛙酶和其他抗癌药物联合应用会增强抗癌药物的抗肿瘤细胞毒性。目前,豹蛙酶对小细胞肺癌和其他实体肿瘤的治疗处于Ⅰ期或Ⅱ期临床试验,对恶性间皮瘤的治疗处于Ⅲ期临床试验阶段,是潜在的治疗恶性间皮瘤的药物。 Onconase, also called P30 protein, is a member of RNase A superfamily, and is the only enzyme of this class that reached clinical trials. It has weak RNase activity and strong cytotoxicity to various tumor cells in vitro as well as in vivo, and it is one of the 100 new drugs in research recently. Onconase was first found in early embryos of leopard frog (Rana pipiens) , and onconase can trigger apoptosis of tumor cells via degrading RNA, leading to inhibiting sythesis of protein. In addition, onconase has other anticancer mechanisms, such as influencing expression of specific genes and destroying telomerase RNA. Onconase could also enhance the cytotoxicity of other anticancer drugs. The phase and phase Ⅰ/Ⅱ clinical trials of onconase as a single therapeutic agent in patients with non-small cell lung cancer and other solid tumors is conducting, and the phase Ⅲ human clinical trials for the treatment of unresectable malignant mesothelioma (MM) is undergoing. Onconase may serve as a second-line therapy for MM.
出处 《解剖学报》 CAS CSCD 北大核心 2012年第4期574-578,共5页 Acta Anatomica Sinica
基金 国家973前期研究专项资助项目(2010CB534905)
关键词 豹蛙酶 核糖核酸酶 肿瘤 细胞毒性 Onconase Ribonuclease Tumor Cytotoxicity
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参考文献32

  • 1Darzynkiewicz Z, Caner SP, Mikulski SM, et al. Cytostatic and cytotoxic effects of Pannon( p-30 Protein) , a novel anticancer agent [J]. Cell Tissue Kinet, 1988, 21(3) :169-182.
  • 2Ardeh W, Mikulski SM, Shogen K. Amino acid sequence of an anti-tumor protein from Rana pipiens oocytes and early embryos [J]. J Biol Chem, 1991, 266(1) :245-251.
  • 3Welker E, Hathaway L, Xu G, et al. Oxidative folding and N- terminal cyclization of onconase[J]. Biochemistry, 2007, 46( 18 ) : 5485 -5493.
  • 4Liao YD, Wang SC, Leu YJ, et al. The structural integrity exerted by N-terminal pyroglutamate is crucial for the cytotoxicity of frog ribonuclease from Rana pipiens[J]. Nucleic Acids Res, 2003, 31 (18) :5247-5255.
  • 5Raines RT. Artificial Nucleases[ M]. Heidelberg: Springer Veda, 2004 : 19-32.
  • 6Kim BM, Kim H, Raines RT, et al. Glycosylation of onconase increases it conformational stability and toxicity for cancer cells[J]. Biochem Biophys Res Commun, 2004, 315 (4) :976-983.
  • 7Rodriquez M, Torrent G, Bosch M, et al. Intracellular pathway of onconase that enables its delivery to the cytosol [J]. J Cell Sci, 2007, 120 ( Pt8 ) : 1405-1411.
  • 8Benito A, Ribo M, Vilanova M. On the track of antitumor ribonucleases [J]. Mol Biosyst, 2005, 1 (4) :294-302.
  • 9Haigis MC, Raines RT. Secretory ribonucleases are internalized by a dynamin-independent endocytic pathway [J]. J Cell Sci, 2003, 116(Pt2) :313-324.
  • 10Wu Y, Mikulski SM, Ardeh W, et al. A cytotoxic ribonuclease. Study of the mechanism of onconase cytotoxlcity[J]. J Biol Chem, 1993, 268(14) :10686-10693.

二级参考文献20

  • 1Mikulski M, Costanzi J, Vogelzang J. Phase Ⅱ trial of a single weekly intravenous dose of ranpirnase in patients with unresectable malignant mesothelioma[J]. J Clinical Oncology, 2002,20(1): 274-281.
  • 2Darzynkiewicz Z, Carter SP, Mikulski SM, et al. Cytostatic and cytotoxic effects of Pannon (P-30 Protein), a novel anticancer agent[J]. Cell Tissue Kinet, 1988,21(3): 169-182.
  • 3Ardelt W, Mikulski SM, Shogen K, et al. Amino acid sequence of an anti-tumor protein from Rana pipiens oocytes and early embryos. Homology to pancreatic ribonucleases [ J ]. J Biol Chem, 1991,266(1):245-251.
  • 4Merlino A, Mazzarella L, Carannante A, et al. The importance of dynamic effects on the enzyme activity: X-ray structure and molecular dynamics of onconase mutants [M]. JBC Paper in Press,2005.2-22.
  • 5Notomista E, Cafaro V, Fusiello R, et al. A Effective expression and purification of recombinant onconase, an antitumor protein [J]. FEBS Lett, 1999,463(3):211-215.
  • 6Leland PA, Ronald TR. Cancer chemotherapy-ribonucleases to the rescue [J]. Chem Bio,2001,8(5):405-413.
  • 7Ilinskaya ON, Koschinski A, Mitkevich VA, et al. Cytotoxicity of RNases is increased by cationization and counteracted by K (Ca)channels[J]. Biochem Biophys Res Commun,2004,314(2):550-554.
  • 8Wu Y, Mikulski SM, Ardelt W, et al. A cytotoxic ribonuclease. Study of the mechanism of onconase cytotoxicity[J]. J Biol Chem, 1993,268(14): 10686-10693.
  • 9Saxena SK, Sirdeshmukh R, Ardelt W, et al. Entry into cells and selective degradation of tRNAs by a cytotoxic member of the RNase A family [J]. J Biol Chem, 2002,277(17): 15142-15146.
  • 10Iordanov MS, Ryabinina OP, Wong J, et al. Molecular determinants of apoptosis induced by the cytotoxic ribonuclease onconase:evidence for cytotoxic mechanisms different from inhibition of protein synthesis [J].Cancer Res,2000,60(7): 1983-1994.

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