Reserpin Hepatosellüler Karsinom Hücrelerinde Doksorubisinin Genotoksik Etkilerini Artırır

Öz

Amaç: Primer karaciğer maligniteleri arasında en sık tanı konulanı hepatosellüler karsinomdur. Tedavideki ilerlemelere rağmen, ilaç direnci gibi zorluklar doksorubisin dahil olmak üzere kemoterapilerin etkinliğini sınırlandırmaktadır. Yapılan çalışmalarda doğal olarak oluşan bir indol alkaloidi olan reserpinin çeşitli malignitelerde antikanser özellikler göstermiştir. Bu çalışmada amacımız, in vitro koşullarda reserpinin hepatosellüler karsinom hücrelerinde doksorubisinin etkinliğini artırıp artırmadığı araştırılmasıdır. Gereç ve Yöntemler: İnsan hepatosellüler kanser hücreleri (HepG2) kültüre edildi. Rezerpinin IC50 değeri MTT testi ile belirlendi. Doksorubisin ve reserpin HepG2 hücrelerine hem ayrı ayrı hem de birlikte uygulandı. DNA hasarı ise alkali comet testi ile değerlendirildi. Bulgular: Doksorubisin ve rezerpin tek başına uygulandığında HepG2 hücrelerinde DNA hasarını anlamlı düzeyde artırdı (p<0,05). Doksorubisin ile birlikte uygulandığında, rezerpin doksorubisinin HepG2 hücreleri üzerindeki genotoksik etkisini anlamlı şekilde artırdı (p<0,05). Sonuç: Reserpin, in vitro ortamda HepG2 hücrelerinde doksorubisinin genotoksik etkilerini artırmıştır. Bu durum, hepatosellüler karsinoma tedavisinde doksorubisinin terapötik etkinliğini artırmak amacıyla reserpinin adjuvan bir tedavi olarak kullanılabileceğini düşündürmektedir. Bu kombinasyonun temel mekanizmalarının ve olası klinik faydalarının daha iyi anlaşılabilmesi için ileri araştırmalara ihtiyaç vardır.

Anahtar Kelimeler

• Hepatosellüler karsinom
• rezerpin
• doksorubisin
• genotoksisite

RESERPINE ENHANCES THE GENOTOXIC EFFECTS OF DOXORUBICIN IN HEPATOCELLULAR CARCINOMA CELLS

Öz

Objective: Hepatocellular carcinoma is the most frequently diagnosed primary liver malignancy. Despite advances in treatment, challenges such as drug resistance limit the effectiveness of chemotherapy, including doxorubicin. Studies have shown that reserpine, a naturally occurring indole alkaloid, has anticancer properties in various malignancies. The aim of this study was to investigate whether reserpine increases the effectiveness of doxorubicin in hepatocellular carcinoma cells under in vitro conditions. Material and Methods: Human hepatocellular carcinoma (HepG2) cells were cultured. The IC50 value of reserpine was determined by the MTT method. Doxorubicin and reserpine were applied to HepG2 cells, both separately and in combination. DNA damage was evaluated by the alkaline comet assay. Results: Doxorubicin and reserpine significantly increased DNA damage in HepG2 cells when applied alone (p<0.05). When administered together with doxorubicin, reserpine significantly increased the genotoxic effect of doxorubicin on HepG2 cells (p<0.05). Conclusion: Reserpine increased the genotoxic effects of doxorubicin on HepG2 cells in vitro. This suggests that reserpine can be used as an adjuvant therapy to increase the therapeutic efficacy of doxorubicin in the treatment of hepatocellular carcinoma. Further studies are needed to better understand the basic mechanisms and possible clinical benefits of this combination.

Anahtar Kelimeler

• Hepatocellular carcinoma
• reserpine
• doxorubicin
• genotoxicity

Kaynakça

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