Abstract
BackgroundProstate 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.MethodsThe 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.ResultsThe 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.ConclusionI131-PSCA-mAb has the potential to become a new targeted therapy drug for the treatment of prostate cancer.
Highlights
Prostate stem cell antigen (PSCA) is upregulated in prostate cancer tissues
The proliferation abilities, apoptosis and invasion abilities of PC-3 and LNCaP cells treated with I131-PSCA-mAb in vitro were measured by methyl thiazolyl tetrazolium (MTT) assay, flow cytometry and transwell culture, respectively
Compared with the control group, the proliferations of PC-3 and LNCaP cells treated with I131-PSCA-mAb, PSCA-mAb or I131-IgG were inhibited to different degrees
Summary
Prostate stem cell antigen (PSCA) is upregulated in prostate cancer tissues. 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. 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. Androgens could contribute to the initial growth of prostate cancer [4]. Saffran et al found that administration of anti-PSCA mAbs could inhibit metastasis to distant sites and restrain the growth of established orthotopic tumor, which could significantly prolong the survival time of tumor-bearing mice [18]. There are few studies on radioimmunotherapy guided by anti-PSCA mAbs for prostate cancer. The interesting area indicating the region of interest has been used in many surveillance systems, such as medical image processing [19]
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