Enhancing effect of bevacizumab in the classic bleomycin, etoposide, cisplatin treatment applied in human testicular germ cell tumors

Year 2025, Volume: 50 Issue: 3, 683 - 692, 30.09.2025

Deniz Koç , Murat Serkant Ünal

https://doi.org/10.17826/cumj.1662892

Abstract

Purpose: This study aimed to evaluate the therapeutic potential of Bevacizumab, a vascular endothelial growth factor (VEGF) inhibitor, in combination with the standard Bleomycin, Etoposide, and Cisplatin (BEP) regimen for the treatment of testicular germ cell tumors (TGCTs). The primary focus was to investigate its ability to enhance treatment efficacy while reducing cytotoxic side effects.
Materials and Methods: The half-maximal inhibitory concentration (IC₅₀) of the BEP regimen was determined in the 1618-K human TGCT cell line and subsequently combined with varying concentrations of Bevacizumab. Cell viability was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Expression levels of VEGF, Bax, Bcl-2, and Caspase-3 were analyzed by immunohistochemistry.
Results: Bevacizumab significantly reduced cell viability in a dose-dependent manner. Bax expression in Group 2 (2.05 ± 1.04) was significantly lower than in the control group (8.63 ± 2.57;). Caspase-3 expression in Group 2 (0.49 ± 0.08) was markedly decreased compared with the control (5.10 ± 3.82), and a similar reduction was also observed in Group 3. Despite the absence of substantial changes in apoptotic markers, the reduction in cell viability suggests that Bevacizumab may act through alternative mechanisms.
Conclusion: By targeting tumor vascularity, Bevacizumab may enhance the therapeutic efficacy of the BEP regimen in TGCT treatment. These findings support the potential role of Bevacizumab as an adjunctive agent in TGCT therapy and highlight the need for further validation through in vivo studies.

Keywords

testicular germ cell tumors , bevacizumab , VEGF , cell culture techniques

Ethical Statement

This study was approved by the Afyon Kocatepe University Human Ethics Committee (AKÜİEK) with the approval number 2017/2/45 on February 3, 2017.

Supporting Institution

This study was supported by the Afyon Health Sciences University Scientific Research Projects (BAP) with the project number 17-SAĞ.BİL-03.

Project Number

2017/2/45

İnsan testis germ hücreli tümörlerinde uygulanan klasik bleomisin, etoposid, sisplatin tedavisinin bevacizumab ile güçlendirilmesinin etkisi

Abstract

Amaç: Bu çalışmanın amacı, testiküler germ hücreli tümörlerin (GCTT) tedavisinde yaygın olarak kullanılan Bleomisin, Etoposid ve Sisplatin (BEP) kombinasyon tedavisinin etkinliğini artırmak ve sitotoksik yan etkilerini azaltmak üzere vasküler endotelyal büyüme faktörü (VEGF) inhibitörü olan Bevacizumab’ın terapötik potansiyelini değerlendirmektir.
Gereç ve Yöntem: 1618-K insan GCTT hücre hattında BEP tedavisinin yarı maksimal inhibitör konsantrasyonu (IC₅₀) belirlendi. Bu doz, farklı konsantrasyonlardaki Bevacizumab ile birlikte uygulandı. Hücre canlılığı 3-(4,5-dimetiltiyazol-2-il)-2,5-difeniltetrazolyum bromür (MTT) testi ile değerlendirildi. VEGF, Bax, Bcl-2 ve Kaspaz-3’ün ekspresyon düzeyleri immünohistokimya tekniği ile incelendi.
Bulgular: Bevacizumab, doz bağımlı olarak hücre canlılığını anlamlı şekilde azaltmıştır. A Bax ekspresyonu Grup 2’de (2,05±1,04) kontrol grubuna (8,63±2,57) göre anlamlı şekilde azalmıştır. Caspase-3 düzeyi Grup 2’de (0,49±0,08) kontrol grubuna (5,10±3,82) göre anlamlı olarak azalmış, Grup 3’te de benzer bir azalma görülmüştür. Apoptotik belirteçlerde anlamlı değişiklik olmamasına rağmen, hücre canlılığındaki azalma Bevacizumab’ın farklı mekanizmalarla etkili olabileceğini göstermektedir.
Sonuç: Bevacizumab’ın tümör vaskülaritesini hedef alarak BEP tedavisinin etkinliğini artırabileceği düşünülmektedir. Bu bulgular, Bevacizumab’ın GCTT tedavisinde destekleyici bir ajan olarak kullanılma potansiyeline işaret etmekte ve in vivo çalışmalarla desteklenmesi gerektiğini göstermektedir.

Keywords

testiküler germ hücre tümörleri , bevacizumab , VEGF , hücre kültürü teknikleri

Ethical Statement

Bu çalışma, Afyon Kocatepe Üniversitesi İnsan Etik Kurulu'ndan (AKÜİEK) 03.02.2017 tarihinde 2017/2/45 numaralı onay ile etik kurul onayı almıştır.

Supporting Institution

Bu çalışma, Afyon Sağlık Bilimleri Üniversitesi Bilimsel Araştırma Projeleri (BAP) tarafından 17-SAĞ.BİL-03 proje numarası ile desteklenmiştir.

Project Number

2017/2/45

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