Novel Application of Cell Penetrating R11 Peptide for Diagnosis of Bladder Cancer
Novel Application of Cell Penetrating R11 Peptide for Diagnosis of Bladder Cancer
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细胞穿透R11肽在膀胱癌诊断中的新应用
DOI：
10.1166/jbn.2018.2499
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发表时间：
2018-01-01
影响因子：
2.9
通讯作者：
Fan, Jinhai
中科院分区：
文献类型：
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作者：
Du, Yiqing;Wang, Lei;Fan, Jinhai
目的：聚精氨酸(R11)作为一种新型的细胞通透性多肽，在膀胱癌的靶向治疗中显示出巨大的潜力。然而，它在BCA和正常膀胱组织之间的诊断能力和摄取效率尚不清楚。在本研究中，我们探讨了异硫氰酸荧光素(FITC-R11)标记的R11用于临床检测BCA的可行性。方法：合成FITC-R11，分别与BCA细胞系(T24、5637、RT4)、正常人永生化膀胱上皮细胞系(SVHUC)及BCA和良性前列腺增生症患者的临床标本孵育。摄取效率由FITC相对强度的平均值决定。此外，将FITC-R11注入裸鼠原位T24-t肿瘤和膀胱癌肺转移模型裸鼠体内，检测膀胱癌和正常膀胱组织以及肺组织的荧光强度。结果：与FITC-R11孵育后，T24、5637、RT4和SVHUC细胞株的荧光强度分别为64678.56+/-9699.27、46456.22+/-2588.06、33802.02+/-429.72和17785.01+/-1704.36(P<0.05)。在裸鼠原位T24-t移植瘤中，FITC-R11在膀胱癌组织中较正常膀胱组织有较高的积聚，在肺转移瘤小鼠的肺组织中也有积聚。此外，胆囊癌组织中FITC-R11的摄取效率显著高于正常膀胱组织(6441.95比1196.92，P<0.05)以及良性前列腺增生患者和良性前列腺增生症患者的尿样(30250.37比4948.42，P<0.05)。结论：与正常膀胱组织相比，FITC-R11是一种更具特异性的BCA分子探针，具有潜在的临床应用价值。
Objective: As a novel cell-permeable peptide, polyarginine (R11) showed great potential as contrast agent to target bladder cancer (BCa) for therapeutic applications. However, its diagnostic ability and uptake efficiency between BCa and normal bladder tissues is unknown. In this study, we investigated the feasibility of R11 conjugated with fluorescein isothiocyanate (FITC-R11) for detecting BCa in clinical practice. Method: FITC-R11 was synthesized and incubated with BCa cell lines (T24, 5637, RT4), normal immortalized human bladder epithelial cell line (SVHUC) and clinical specimens from BCa and benign prostate hyperplasia patients. The uptake efficiency was determined by the mean values of relative FITC intensity. Furthermore, FITC-R11 was intravesically injected into the athymic nude mice bearing orthotopic T24-t tumors and pulmonary metastasis of bladder tumor mice models, the fluorescence intensity of bladder tumors and normal bladder tissues was examined, as well as lung tissues. Result: After incubation with FITC-R11, the fluorescence intensity of T24, 5637, RT4 and SVHUC cell line was 64678.56 +/- 9699.27, 46456.22 +/- 2588.06, 33802.02 +/- 429.72 and 17785.01 +/- 1704.36, respectively (P < 0.05). In the athymic nude mice bearing orthotopic T24-t tumors, FITC-R11 showed elevated accumulation in the bladder tumors compared with normal bladder tissues, FITC-R11 was also accumulated in the lung of pulmonary metastasis mice. Moreover, the uptake efficiency of FITC-R11 in patients' BCa tissues was much higher than in normal bladder tissues (6441.95 vs. 1196.92, P < 0.05), as well as the urine samples of BCa patients and benign prostate hyperplasia patients (30250.37 vs. 4948.42, P < 0.05). Conclusion: As compared with normal bladder tissue, FITC-R11 is a more specific molecular probe for BCa, and has the potential application in clinical practice.