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<p>Embryonal carcinoma is a type of aggressive testicular cancer, specifically a non-seminomatous germ cell tumor, that tends to grow rapidly and spread outside the testicle. Bleomycin and etoposide are the most common chemotherapy combinations for this cancer. This study aimed to investigate inhibitory effects of bleomycin and etoposide combination on proliferation and migration of NCCITs as embryonal carcinoma cells. According to the MTT assay, bleomycin and etoposide showed cytotoxic effect with IC<sub>50</sub> values of 127 and 105&#xa0;μM respectively. The combination of bleomycin and etoposide at a fixed molar ratio of 1:1 produced an additive cytotoxic effect (IC<sub>50</sub>: 55&#xa0;μM for each drug) as demonstrated by combination index calculation and isobologram analysis using CompuSyn software. In combination therapy, bleomycin and etoposide indicate favorable dose reduction vs. as a single drug (DRI &gt; 1). According to real time PCR analysis, combination of etoposide and bleomycin for 48&#xa0;h reduced expression of epithelial-mesenchymal transition (EMT)-related markers; vimentin (80%), snail (64%) and MMP-9 (86%) and pluripotency-associated genes; OCT4 (94%), NANOG (83%) and SOX2 (72%). Scratch wound healing assay and transwell migration assay indicated anti-migratory effect of bleomycin and etoposide combination on NCCIT cells. In conclusion, combination of bleomycin and etoposide is effective for suppressing proliferation and migration of embryonal carcinoma testicular cancer cells. This approach could enhance therapeutic efficacy by overcoming tumor resistance, increasing cancer cell kill through distinct mechanisms of action, and minimizing overlapping toxicities.</p>

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Etoposide and Bleomycin Combination Additively Inhibit Proliferation and Migration of Germ Cell Tumors In Vitro

  • 期刊论文

  • 发表日期：

    2026年7月20日

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  • Sara Soltanian,
  • Zahra Movahedi,
  • Behjat Kalantari Khandani

摘要

Embryonal carcinoma is a type of aggressive testicular cancer, specifically a non-seminomatous germ cell tumor, that tends to grow rapidly and spread outside the testicle. Bleomycin and etoposide are the most common chemotherapy combinations for this cancer. This study aimed to investigate inhibitory effects of bleomycin and etoposide combination on proliferation and migration of NCCITs as embryonal carcinoma cells. According to the MTT assay, bleomycin and etoposide showed cytotoxic effect with IC50 values of 127 and 105 μM respectively. The combination of bleomycin and etoposide at a fixed molar ratio of 1:1 produced an additive cytotoxic effect (IC50: 55 μM for each drug) as demonstrated by combination index calculation and isobologram analysis using CompuSyn software. In combination therapy, bleomycin and etoposide indicate favorable dose reduction vs. as a single drug (DRI > 1). According to real time PCR analysis, combination of etoposide and bleomycin for 48 h reduced expression of epithelial-mesenchymal transition (EMT)-related markers; vimentin (80%), snail (64%) and MMP-9 (86%) and pluripotency-associated genes; OCT4 (94%), NANOG (83%) and SOX2 (72%). Scratch wound healing assay and transwell migration assay indicated anti-migratory effect of bleomycin and etoposide combination on NCCIT cells. In conclusion, combination of bleomycin and etoposide is effective for suppressing proliferation and migration of embryonal carcinoma testicular cancer cells. This approach could enhance therapeutic efficacy by overcoming tumor resistance, increasing cancer cell kill through distinct mechanisms of action, and minimizing overlapping toxicities.