Recombinant lysyl oxidase propeptide protein inhibits growth and promotes apoptosis of pre-existing murine breast cancer xenografts.
Recombinant lysyl oxidase propeptide protein inhibits growth and promotes apoptosis of pre-existing murine breast cancer xenografts.
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DOI：
10.1371/journal.pone.0031188
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Trackman PC
中科院分区：
文献类型：
--
作者：
Bais MV;Nugent MA;Stephens DN;Sume SS;Kirsch KH;Sonenshein GE;Trackman PC
赖氨酸氧化酶前肽（LOX-PP）异位过表达抑制肿瘤异种移植物生长。本研究确定了纯化的重组LOX-PP （rLOX-PP）蛋白抑制已存在的异种移植物生长的能力和作用方式。实验方法是直接瘤内注射rLOX-PP蛋白到小鼠乳腺癌NF639异种移植物中，并在NCR nu/nu小鼠肿瘤附近植入rLOX-PP缓释制剂（n = 10）。监测肿瘤的生长情况，并在牺牲后进行免疫组织化学和Western blot分析增殖，凋亡和rLOX-PP本身的几种标志物。与对照组相比，直接注射rLOX-PP显著减少了第20、22和25天的肿瘤体积和第25天收获时的肿瘤重量30%。体内植入35微克rLOX-PP微球（n = 10），与空微球相比，牺牲了肿瘤体积和重量（p<0.05）。植入后第22、25天肿瘤体积缩小30% (p<0.05)，第25天最终肿瘤重量缩小30% (p<0.05)，肿瘤生长速率降低60%。rLOX-PP显著降低了增殖标志物的表达和Erk1/2 MAP激酶的激活，而凋亡标志物的表达明显增加。免疫组织化学检测rLOX-PP在收获的rLOX-PP肿瘤中，而在对照组中未检测到rLOX-PP。数据提供临床前研究结果，支持rLOX-PP蛋白制剂治疗抗癌潜力的原理证明。
Lysyl oxidase propeptide (LOX-PP) ectopic overexpression inhibits the growth of cancer xenografts. Here the ability and mode of action of purified recombinant LOX-PP (rLOX-PP) protein to inhibit the growth of pre-existing xenografts was determined. Experimental approaches employed were direct intratumoral injection (i.t.) of rLOX-PP protein into murine breast cancer NF639 xenografts, and application of a slow release formulation of rLOX-PP implanted adjacent to tumors in NCR nu/nu mice (n = 10). Tumors were monitored for growth, and after sacrifice were subjected to immunohistochemical and Western blot analyses for several markers of proliferation, apoptosis, and for rLOX-PP itself. Direct i.t. injection of rLOX-PP significantly reduced tumor volume on days 20, 22 and 25 and tumor weight at harvest on day 25 by 30% compared to control. Implantation of beads preloaded with 35 micrograms rLOX-PP (n = 10) in vivo reduced tumor volume and weight at sacrifice when compared to empty beads (p<0.05). A 30% reduction of tumor volume on days 22 and 25 (p<0.05) and final tumor weight on day 25 (p<0.05) were observed with a reduced tumor growth rate of 60% after implantation. rLOX-PP significantly reduced the expression of proliferation markers and Erk1/2 MAP kinase activation, while prominent increases in apoptosis markers were observed. rLOX-PP was detected by immunohistochemistry in harvested rLOX-PP tumors, but not in controls. Data provide pre-clinical findings that support proof of principle for the therapeutic anti-cancer potential of rLOX-PP protein formulations.
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影响因子：
4
作者：
Min, Chengyin;Zhao, Yingshe;Romagnoli, Mathilde;Trackman, Philip C.;Sonenshein, Gail E.;Kirsch, Kathrin H.
通讯作者：
Kirsch, Kathrin H.
影响因子：
3.7
作者：
Bondareva A;Downey CM;Ayres F;Liu W;Boyd SK;Hallgrimsson B;Jirik FR
通讯作者：
Jirik FR
DOI：
10.1073/pnas.90.4.1513
发表时间：
1993-02-15
影响因子：
11.1
作者：
EDELMAN, ER;NUGENT, MA;KARNOVSKY, MJ
通讯作者：
KARNOVSKY, MJ
影响因子：
50.5
作者：
Guarneri, V.;Piacentini, F.;Conte, P.
通讯作者：
Conte, P.
影响因子：
56.9
作者：
Kessler, E;Takahara, K;Greenspan, DS
通讯作者：
Greenspan, DS