Silmarin nöroblastom hücrelerinde pro-inflamatuvar sitokin üretimini düzenleyerek sisplatin ile birlikte hücre ölümünü etkiler mi?

Amaç: Nöroblastom çocukluk çağında en sık görülen ekstrakraniyal solid tümördür. Sisplatin çocukluk çağı kanserlerinde yaygın bir şekilde kullanılmaktadır. Silmarin "milk thistle"dan ekstrakte edilen bir poliflavonoid bileşiktir. Pro-inflamatuvar sitokinlerin nöroblastomda tümör gelişimi ve metastazında rolleri vardır. Bu çalışmanın amacı, nöroblastom hücrelerinde silmarinin tek başına ve sisplatin ile birlikte kullanılmaları durumunda anti-tümoral ve proinflamatuvar sitokin üretimi üzerindeki etkilerinin değerlendirilmesidir. Yöntemler: C1300 fare nöroblastom hücreleri 37°C %5 CO2 ve DMEM hücre çoğaltma ortamı kullanılarak çoğaltıldı. Hücrelere silmarin, sisplatin ve silmarin-sisplatin kombinasyonu uygulandı ve hücre canlılığı üzerindeki etkisi WST-1 ve apoptotik hücre ölümü akış sitometrik olarak anneksin-V/PI testi ile değerlendirildi. Pro-inflamatuvar sitokinler olan IL-6, IL-1b ve TNF-? düzeyleri fare ELISA testleri kullanılarak ölçüldü. Gruplar arasındaki farklar SPSS 15.0 programında Kruskall-Wallis ve Mann-Whithney-U analizi ile değerlendirildi ve p

Does silymarin combined with cisplatin affect neuroblastoma cell death via pro-inflammatory cytokine production?

Objective: Neuroblastoma is the most common extracranial solid tumor in childhood. Cisplatin is widely used in pediatric malignancies. Silymarin is a polyflavonoid compound extracted from "milk thistle". Pro-inflammatory cytokines have a role in tumor growth and metastases of neuroblastoma cells. The aim of this study was to evaluate effects of silymarin alone or in combination with cisplatin on the production of antitumoral and pro-inflammatory cytokine in neuroblastoma cells.Methods: C1300 mouse neuroblastoma cells were grown with DMEM medium in 37°C and 5% CO2 conditions. The cells were treated with silymarin, cisplatin and silymarin-cisplatin combinations and cell viability was evaluated using WST-1 and apoptotic cell death with flow cytometric annexin-V/PI tests. Levels of pro-inflammatory cytokines of IL-6, IL-1b and TNF-? were measured with mouse ELISA kits. Differences between the groups were evaluated with KruskallWallis and Mann-Whitney-U analysis in SPSS 15.0 program and p<0.05 was accepted as a level of statistically significant. Results: Silymarin reduced the cell viability in a dose-dependent manner when compared with control. Silymarin-cisplatin combination greatly reduced viability of cells compared with cisplatin alone. Cisplatin increased the level of pro-inflammatory cytokines. Pro-inflammatory cytokine levels did not change with silymarin alone. Combinations of silymarin and cisplatin decreased pro-inflammatory cytokine levels except IL-1b when compared with cisplatin alone. Conclusion: Our results indicated that Silymarin is a potential anti-tumoral agent alone and in combination with cisplatin. Anti-tumoral effects of this combination possibly realized by decreasing pro-inflammatory cytokine levels. Anti-tumoral effect and mechanisms of silymarin should be proven by testing them on the in-vivo animal models.

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