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I131-PSCA-mAb 在前列腺癌原位模型小鼠中的治疗效果。

The therapeutic efficacy of I131-PSCA-mAb in orthotopic mouse models of prostate cancer.

机构信息

Department of Urology, Yantai Yuhuangding Hospital Affiliated to Medical College of Qingdao University, NO,20 East Yuhuangding Road, 264000 Yantai, China.

出版信息

Eur J Med Res. 2013 Dec 13;18(1):56. doi: 10.1186/2047-783X-18-56.

DOI:10.1186/2047-783X-18-56
PMID:24330823
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3878678/
Abstract

BACKGROUND

Prostate stem cell antigen (PSCA) is upregulated in prostate cancer tissues. Here we aimed to study the therapeutic efficacy of a monoclonal antibody of PSCA-labeled I131 (I131-PSCA-mAb) in orthotopic mouse models of prostate cancer.

METHODS

The proliferation, apoptosis and invasion abilities of PC-3 and LNCaP cells treated with I131-PSCA-mAb were measured by methyl thiazolyl tetrazolium assay, flow cytometry and transwell culture, respectively. The human prostate cancer models were established by orthotopic implantation of PC-3 and LNCaP cells in nude mice. I131-PSCA-mAb distribution and tumor cell apoptosis in the tumor-bearing nude mice were measured.

RESULTS

The inhibitory and apoptosis rates of PC-3 and LNCaP cells treated with I131-PSCA-mAb reached a maximum of 84%, 80% and 50%, 46%, respectively, which were obviously higher than in the cells treated with I131-IgG or PSCA-mAb. The invaded number of PC-3 and LNCaP cells treated with I131-PSCA-mAbe was significantly reduced (P < 0.01) compared with the control group. The ratios of I131-PSCA-mAb in tumor to intramuscular I131-PSCA-mAb (T/NT) in tumor-bearing nude mice were increased with time and reached the highest level after 8 h. T/NT stayed above 3.0 after 12 h, and the tumor could still be developed after 24 h. The number of apoptotic cells in tumor tissue of nude mice treated with I131-PSCA-mAb was larger than that in the control group.

CONCLUSION

I131-PSCA-mAb has the potential to become a new targeted therapy drug for the treatment of prostate cancer.

摘要

背景

前列腺干细胞抗原（PSCA）在前列腺癌组织中上调。本研究旨在探讨 PSCA 标记的单克隆抗体 I131-PSCA-mAb 在前列腺癌原位模型小鼠中的治疗效果。

方法

采用噻唑蓝比色法、流式细胞术和 Transwell 培养分别检测 I131-PSCA-mAb 处理的 PC-3 和 LNCaP 细胞的增殖、凋亡和侵袭能力。通过将 PC-3 和 LNCaP 细胞原位植入裸鼠建立人前列腺癌模型。检测荷瘤裸鼠中 I131-PSCA-mAb 的分布和肿瘤细胞凋亡。

结果

I131-PSCA-mAb 处理的 PC-3 和 LNCaP 细胞的抑制率和凋亡率分别达到 84%、80%和 50%、46%，明显高于 I131-IgG 或 PSCA-mAb 处理的细胞。I131-PSCA-mAb 处理的 PC-3 和 LNCaP 细胞的侵袭数量明显减少（P < 0.01）。荷瘤裸鼠中 I131-PSCA-mAb 在肿瘤与肌肉内 I131-PSCA-mAb（T/NT）的比值随时间增加，8 h 时达到最高水平。12 h 后 T/NT 仍保持在 3.0 以上，24 h 后肿瘤仍可显影。I131-PSCA-mAb 处理的裸鼠肿瘤组织中的凋亡细胞数量多于对照组。

结论

I131-PSCA-mAb 有可能成为治疗前列腺癌的一种新的靶向治疗药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d38/3878678/c46056a7b103/2047-783X-18-56-6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d38/3878678/8221a9aa87a6/2047-783X-18-56-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d38/3878678/ee3f7bf3c0bd/2047-783X-18-56-2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d38/3878678/e8eb148666ee/2047-783X-18-56-3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d38/3878678/2ebb1d33a4cf/2047-783X-18-56-4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d38/3878678/5023abf7eee1/2047-783X-18-56-5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d38/3878678/c46056a7b103/2047-783X-18-56-6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d38/3878678/8221a9aa87a6/2047-783X-18-56-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d38/3878678/ee3f7bf3c0bd/2047-783X-18-56-2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d38/3878678/e8eb148666ee/2047-783X-18-56-3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d38/3878678/2ebb1d33a4cf/2047-783X-18-56-4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d38/3878678/5023abf7eee1/2047-783X-18-56-5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d38/3878678/c46056a7b103/2047-783X-18-56-6.jpg

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