The objective was to investigate the antitumor effect of F3-PE39KDEL in vitro and in vivo. MTT method was employed to determine the inhibiting effect of F3-PE39KDEL on MCF-7, A549, SKOV3 and HepG2 cell lines. Its toxicity in mice was observed using the median lethal dose method. Its antitumor effect was determined based on the transplanted A549 cell line in nude mice. The results showed that when the culture times were 72 h and 120 h, the F3-PE39KDEL showed significant inhibitory effect on A549 and MCF-7 cell lines, with IC50 values of 0.41 and 0.42 μg/mL, and 4.95 and 2.53 μg/mL, respectively. The toxicity test showed that the median lethal dose was 1.1782 mg/kg. The animals' spontaneous movement was decreased after administration, and animals died mainly within 1d after administration. All the animals including the dead and alive showed no abnormalities after sectional examination. The F3-PE39KDEL showed a potential antitumor effect in vivo. At the doses of 0.1, 0.2 and 0.4 mg/kg, its inhibitory rates were 37.0%, 43.2% and 53.1%, respectively, and the dose-activity relationship was also observed. These results suggest that the F3-PE39KDEL has good prospects in terms of targeted cancer therapy.
GUO Kai
,
WANG Yilian
,
ZHOU Hongzi
,
CHEN Quan
,
CHEN Kai
,
LI Jishun
,
HU Jindong
,
YANG Hetong
. Recombinant Vascular Endothelial Receptor F3 Peptide-PE39KDEL Protein can Inhibit Tumor Growth[J]. Science & Technology Review, 2014
, 32(7)
: 15
-21
.
DOI: 10.3981/j.issn.1000-7857.2014.07.001
[1] Folkman J. Angiogenesis in cancer, vascular, rheumatoid and other disease[J]. Nature Medicine, 1995, 1(1): 27-30.
[2] 吴学萍, 谢明均, 孙艳, 等. 短肽修饰的甲氨蝶呤的制备及细胞毒性作 用[J]. 中国医院药学杂志, 2011, 31(1): 32-35. Wu Xueping, Xie Mingjun, Sun Yan, et al. Preparation of methotrexate modified by small peptide and study on its cytotoxic effect[J]. Chinese Journal of Hospital Pharmacy, 2011, 31(1): 32-35.
[3] 周雅梅, 吴学萍, 曾理, 等. 肽修饰的的甲氨蝶呤体外抗肿瘤作用初步 研究[J]. 药学学报, 2012, 47(4): 452-458. Zhou Yamei, Wu Xueping, Zeng Li, et al. In vitro anti-tumor effect of methotrexate modified by peptide[J]. Acta Pharmaceutica Sinica, 2012, 47(4): 452-458.
[4] Porkka K, Laakkonen P, Hoffman J A, et al. A fragment of the HMGN2 protein homes to the nuclei of tumor cells and tumor endothelial cells in vivo[J]. Proceedings of the National Academy of Sciences, 2002, 99 (11): 7444-7449.
[5] Grinstein E, Shan Y, Karawajew L, et al. Cell cycle- controlled interaction of nucleolin with the retinoblastoma protein and cancerous cell transformation[J]. Journal of Biological Chemistry, 2006, 281(31): 22223-22235.
[6] Yates S P, Merrill A R. A catalytic loop within pseudomonas aeruginosa exotoxin A modulates its transferase activity[J]. Journal of Biological Chemistry, 2001, 276 (37): 35029-35036.
[7] Yates S A S P, Merrill A R. Insight into the catalytic mechanism of pseudomonas aeruginosa exotoxin A[J]. Biochemistry, 2002, 277(48): 46669-46675.
[8] 祁志荣, 李虹. PE类重组免疫毒素的研究进展[J]. 微生物学免疫学进 展, 2006, 34(1): 50-53. Qi Zhirong, Li Hong. Advances in recombinant immunotoxin of PE class[J]. Progress in Microbiology and Immunology, 2006, 34(1): 50-53.
[9] 张艳, 刘秀群. 高效低毒的系列功能蛋白: 中国, 200410033621.6[P]. 2004-10-03. Zhang Yan, Liu Xiuqun. Series functional protein of high efficiency and low toxicity: CN, 200410033621.6[P]. 2004-10-03.
[10] Taupiac M P, Bébien M, Alami M, et al. A deletion within the translocation domain of pseudomonas exotoxin A enhances translocation efficiency and cytotoxicity concomitantly [J]. Molecular Microbiology, 1999, 31(5): 1385-93.
[11] Fitzgerald D J. Pastan I H. Recombinant pseudomonas exotoxin with increased activity: US, 5821238 A[P]. 1998-10-13.
[12] 朱海兵, 黄轶, 曾昭淳. F3重组毒素的克隆表达及纯化[J]. 科技导 报, 2009, 27(12): 19-22. Zhu Haibing, Huang Yi, Zeng Zhaochun. The cloning, expression and purification of F3 recombinant toxin [J]. Science & Technology Review, 2009, 27(12): 19-22.
[13] 刘新, 邵长伦, 孔雯, 等. 中药复方海藻制剂体外免疫调节、细胞毒和 抗氧化作用[J]. 中国海洋药物, 2009, 28(4): 13-16. Liu Xin, Shao Changlun, Kong Wen, et al. Immunomodulatory, cytotoxic and antioxidant effects of traditional Chinese medicine seaweed complex prescription in vitro[J]. Chinese Journal of Marine Drugs, 2009, 28(4): 13-16.
[14] Thundimadathil J. Cancer treatment using peptides: Current therapies and future prospects [J]. Journal of Amino Acids, 2012, 2012: doi: 10.1155120121967347.
[15] Winer I, Wang S, Lee Y E, et al. F3-targeted cisplatin-hydrogel nanoparticles as an effective therapeutic that targets both murine and human ovarian tumor endothelial cells in vivo [J]. Cancer Research, 2010, 70(21): 8674-83.
[16] 郭凯,赵晓燕,周红姿, 等. 重组人促性腺激素-铜绿假单胞菌外毒素 A蛋白的可溶性表达、纯化和对肿瘤细胞的抑制活性[J]. 山东科学, 2013, 26(2): 41-47. Guo Kai, Zhao Xiaoyan, Zhou Hongzi, et al. Soluble expression and purification of GnRH-PE39KDEL and the inhibition to the activity of a tumor cell [J]. Shandong Science, 2013, 26(2): 41-47.
