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抗前列腺癌多肽APP216的体外活性 被引量：1

In vitro activity of an anti-prostate cancer polypeptide APP216
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摘要 目的:探讨抗前列腺癌多肽APP216对体外培养的前列腺癌细胞的杀伤作用,为抗前列腺癌新药的研究奠定基础。方法:利用MTT实验、细胞凋亡染色及流式细胞仪,检测包含有BH3、K237、DG2结构域和能被PSA特异性水解的短肽序列的多肽药物APP216对分泌PSA的前列腺癌细胞系LNCaP、22RV1及不分泌PSA的前列腺癌细胞系PC3m、DU145的杀伤作用。结果:APP216(270μg/ml)处理48h后,前列腺癌细胞系LNCaP、22RV1的细胞生存率分别为22%和34%,72h后为10%和8%;前列腺癌细胞系PC3m、DU145的细胞生存率分别为90%和95%,72h后为87%和92%。APP216作用后,分泌PSA的前列腺癌细胞胞核呈致密浓染,或呈碎块状,有凋亡小体出现;不分泌PSA的PC3m细胞则未发现改变。APP216(270μg/ml)处理48h后,分泌PSA的LNCaP细胞凋亡率为36.26%,不分泌PSA的PC3m细胞凋亡率仅为1.63%。结论:APP216多肽对分泌PSA的前列腺癌细胞有杀伤作用,可诱导肿瘤细胞发生凋亡;而对于不分泌PSA的前列腺癌细胞则效果不佳。证实了该多肽可被PSA特异性酶切;同时,BH3结构域可通过HIV-TAT的转导作用转入细胞内诱导凋亡。 Objective： To investigate the in vitro the anti-prostate cancer effect of a novel polypeptide, APP216, so as to provide a basis for development of new drug for treatment of prostate cancer. Methods： The polypeptide drug included the amino sequences of BH3, K237 and DG2 domain and the peptide that could be digested by PSA. The anti-prostate cancer effects of the polypeptide prodrug on prostate cancer cell line LNCaP, 22RV1 （secreting PSA） and PC3, DU145 （secreting no PSA） were determined by MTT test and Hoechst 33258 staining. Results： MTT test revealed that the surviving rates of LNCaP and 22PV1 cells were respectively 22% and 34% 48 h after APP216 （270 μg/ml） treatment, and 9. 8% and 8.2% 72 h after APP216 （270 μg/ml） treatment. The surviving rates of PC3 and DU145 cells were respectively 90% and 95% 48 h after APP216 （270 μg/ml） treatment, and 87% and 92% 72 h after APP216 （270 μg/ml） treatment. Hoechst 33258 staining showed the typical features of cell apoptosis： cell shrinkage, chromatin condensation and hypodiploid genomic DNA content in LNCaP and PC3m cells. Flow cytometry showed an apotosis rate of 36.26% 48 h after APP216 （270 μg/ml） treatment in LNCaP cells, and of 1.63% after 48 h APP216 （270 μg/ml） treatment in PC3m cells. Conclusion： APP216 has a satisfactory in vitro cytotoxicity on human PSA - secreting prostate cancer cells and can induce tumor cell apoptosis, but not on non-PSA secreting prostate cancer cells, indicating APP216 polypeptide can be specifically digested by endonuclease enzyme. Meanwhile, BH3 domain can be transferred into cells and induce apoptosis through HIV-TAT.
作者 李斌 郝晓柯 李立文 苏明权
机构地区 第四军医大学西京医院检验科 第四军医大学西京医院全军骨科研究所
出处 《中国肿瘤生物治疗杂志》 CAS CSCD 2006年第3期205-208,共4页 Chinese Journal of Cancer Biotherapy
基金 国家高新技术研究发展规划(863)资助项目(NO.2001AA215321)
关键词 多肽 前列腺癌 活性 凋亡 polypeptide prostate cancer activation apoptosis
分类号 R737.25 [医药卫生—肿瘤]
  • 相关文献

参考文献9

  • 1Jemal A,Siegel R,Ward E.Cancer statistics,2006[J].CA Cancer J Clin,2006,56(2):106-130.
  • 2Balk SP,Ko YJ,Bubley GJ.Biology of prostate-specific antigen[J].J Clin Oncol,2003,21(2):383-391.
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  • 4李斌,郝晓柯,苏明权.PSA激活的前体药物疗法治疗前列腺癌研究进展[J].中国肿瘤生物治疗杂志,2004,11(2):154-156. 被引量：4
  • 5Bouillet P,Strasser A.BH3-only proteins evolutionarily conserved proapoptotic Bcl-2 family members essential for initiating programmed cell death[J].J Cell Sci,2002,115(8):1567-1574.
  • 6Hetian L,Ping A,Shumei S,et al.A Novel peptide isolated from a phage display library inhibits tumor growth and metastasis by blocking the binding of vascular endothelial growth factor to Its kinase domain receptor[J].J Biol Chem,2002,277 (45):43137-43142.
  • 7Yayon A,Aviezer D,Safran M,et al.Isolation of peptides that inhibit binding of basic fibroblast growth factor to its receptor from a random phage-epitope library[J].Proc Natl Acad Sci USA,1993,90(22):10643-10647.
  • 8李斌,郝晓柯,李立文,苏明权,姜南艳.抗前列腺癌多肽融合蛋白在大肠杆菌中的原核表达[J].第四军医大学学报,2005,26(9):796-798. 被引量：4
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二级参考文献24

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共引文献5

同被引文献10

  • 1李斌,郝晓柯,苏明权.PSA激活的前体药物疗法治疗前列腺癌研究进展[J].中国肿瘤生物治疗杂志,2004,11(2):154-156. 被引量：4
  • 2李斌,郝晓柯,李立文,苏明权,姜南艳.抗前列腺癌多肽融合蛋白在大肠杆菌中的原核表达[J].第四军医大学学报,2005,26(9):796-798. 被引量：4
  • 3Balk SP, Ko YJ, Bubley GJ. Biology of prostate-specific antigen[J]. J Clin Oncol, 2003, 21(2) :383-391.
  • 4Brady SF, Pawluczyk JM, Lumma PK, et, al. Design and synthesis of a pro-drag of vinblastine targeted at treatment of prostate cancer with enhanced efficacy and reduced systemic toxicity [J].J Med Chem,2002, 45(21):4706-4715.
  • 5Bouiilet P, Strasser A. BH3-only proteins - evolutionarily conserved proapoptotic Bcl-2 family members essential for initiating programmed cell death [J]. J Cell Sci,2002, 115(8):1567-1574.
  • 6Hetian L, Ping A, Shumei S, et al. A Novel peptide isolated from a phage display library inhibits tumor growth and metastasis by blocking the binding of vascular endothelial growth factor to Its kinase domain receptor [J]. J Biol Chem, 2002, 277 (45):43137-43142.
  • 7Yayon A, Aviezer D, Safran M, et al. Isolation of peptides that inhibit binding of basic fibroblast growth factor to its receptor from a random phage-epitope library [J]. Proc Natl Acad Sci USA,1993, 90(22):10643-10467.
  • 8Sano M, Tatsumi N. Electro chemiluminescence immunoassay[J]. Rinsho Byori, 1996,44 (11): 1076-1079.
  • 9Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2006[J].CA Cancer J Clin,2006, 56(2):106-130.
  • 10Renner M. Inverted chemistry-from drug to prodrug[J]. Trends Mol Med,2001,7(3):100.

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中国肿瘤生物治疗杂志
2006年 第3期

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