Epidermal Growth Factor Based Targeted Toxin for the Treatment of Bladder Cancer

被引：4

作者：

Masilamani, Anie Priscilla ^{[1
,2
]}

Fischer, Alexandra ^{[1
,2
]}

Schultze-Seemann, Susanne ^{[1
,2
]}

Kuckuck, Irina ^{[1
,2
]}

Wolf, Isis ^{[1
,2
]}

Dressler, Franz Friedrich ^{[3
]}

Gratzke, Christian ^{[1
,2
]}

Wolf, Philipp ^{[1
,2
]}

机构：

[1] Univ Freiburg, Fac Med, Freiburg, Germany

[2] Univ Freiburg, Based Diagnost & Therapies Med Ctr, Dept Urol, Freiburg, Germany

[3] Univ Med Ctr Schleswig Holstein, Inst Pathol, Lubeck, Germany

来源：

ANTICANCER RESEARCH | 2021年 / 41卷 / 08期

关键词：

Bladder cancer; epidermal growth factor; epidermal growth factor receptor; targeted toxin; Pseudomonas Exotoxin A; PHASE-II TRIAL; FACTOR RECEPTOR; UROTHELIAL CARCINOMA; RADICAL CYSTECTOMY; IN-VITRO; THERAPY; COMBINATION; GEMCITABINE/CISPLATIN; IMMUNOTOXIN; EXPRESSION;

D O I：

10.21873/anticanres.15165

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background/Aim: Reports on over-expression of the epidermal growth factor receptor (EGFR) in bladder cancer and its function in tumorigenesis have suggested to target this antigen. Materials and Methods: We generated the targeted toxin EGF-PE40 consisting of the human epidermal growth factor (EGF) as the binding domain and PE40, a truncated version of Pseudomonas Exotoxin A, as the toxin domain. EGF-PE40 was tested on EGFR-expressing bladder cancer cells in view of binding via flow cytometry, and cytotoxicity via WST viability assay. Induction of apoptosis was examined by western blot. Results: The targeted toxin specifically triggered cytotoxicity in the bladder cancer cells with 50% inhibitory concentration (IC50) values in the low nanomolar or picomolar range, and was about 1,250-to 1,500-fold more cytotoxic than the EGFR inhibitor erlotinib. Cytotoxicity of EGF-PE40 was based on the induction of apoptosis. Conclusion: EGF-PE40 represents a promising candidate for the future treatment of bladder cancer.

引用

页码：3741 / 3746

页数：6

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