Melissa officinalis Ekstraktı Apoptotik Sinyallemeyi Engelleyerek Osimertinibin KHDAK Hücrelerindeki Antiproliferatif Etkinliğini Azaltmaktadır

Year 2025, Volume: 40 Issue: 3, 447 - 464, 31.10.2025

Esra Tuba Sezgin , Murat Çankaya

Abstract

Dünyada kansere bağlı ölümlerin başında küçük hücreli dışı akciğer kanseri (KHDAK) gelmektedir. Tedavide görülen en önemli problem; epidermal büyüme faktörü reseptörü (EGFR) aktive edici mutasyonlardan olan EGFR T790M direnç mutasyonlarını seçici olarak inhibe eden geri dönüşsüz ve üçüncü nesil bir EGFR-tirozin kinaz inhibitörü (TKİ) olan osimertinibe karşı zamanla gelişen dirençtir. Bazı fitokimyasalların kanser hücrelerinin ilaç direncini aşabileceğine dair birçok çalışma bulunmaktadır. Yine ilaçlara göre daha az yan etkiye sahip olmaları da bitkileri kanser tedavisinde popüler hale getirmiştir. Melissa officinalis (M. officinalis) de çeşitli kanser türlerinin tedavisinde yaygın olarak kullanılmakta olan antiproliferatif özellikleri nedeniyle pek çok insan kanser hücre hattında çalışılmış ve anlamlı sonuçlar elde edilmiştir. Bu çalışmada PC-9 KHDAK hücre hattı üzerinde M. offıcinalis bitki ekstraktı ve osimertinibin sinerjik antikanser etkisi incelenmiştir. CompuSyn yazılımı kullanılarak MTT yöntemi ile alınan sonuçların hesaplanmasına göre 50 nM osimertinib ve 50 µg ml-1 M. officinalis metanol ekstresi kombinasyonu PC-9 hücrelerinde 48 saatlik inkübasyon sonunda en iyi antagonisitk etkiyi (CI: 3031.44) göstermiştir. Bu konsantrasyon kombinasyonunda BCL-2 ilişkili X proteini (BAX), B-hücreli lenfoma 2 (BCL-2) ve Kaspaz 3 (CASP3) gen ifade seviyeleri ve protein düzeyleri sırasıyla RT-qPCR ve ELISA yöntemi ile belirlenmiştir. Ve sonuçlar gösterdi ki, bu kombinasyon PC-9 hücre hattında intrinsik apoptotik yolağı inaktive etmiştir.

Keywords

Akciğer kanseri , Kemoresistans , Melissa officinalis , Osimertinib

Melissa officinalis Extract Reduces the Antiproliferative Efficacy of Osimertinib in NSCLC Cells by Inhibiting Apoptotic Signaling

Abstract

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related deaths worldwide. The most significant problem in treatment is the resistance that develops over time against osimertinib (OSI), an irreversible, third-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) that selectively inhibits EGFR T790M resistance mutations, which are among the activating mutations of the EGFR. Many studies have shown that certain phytochemicals can overcome drug resistance in cancer cells. Additionally, the fact that they have fewer side effects compared to drugs has made plants popular in cancer treatment. Melissa officinalis (M. officinalis) is a plant with antiproliferative properties widely used in the treatment of various cancer types, having shown significant results in many human cancer cell lines. In this study, the antagonistic anticancer effect of M. officinalis plant extract and osimertinib was investigated on the PC-9 NSCLC cell line. According to the calculation of the results obtained by the MTT method using CompuSyn software, the combination of 50 nM osimertinib and 50 µg ml-1 M. officinalis methanol extract showed the best antagonistic effect (CI: 3031.44) after 48h of incubation in PC-9 cells. The gene expression levels and protein levels of BCL-2 associated X protein (BAX), B-cell lymphoma 2 (BCL-2) and Caspase 3 (CASP3) were determined at this concentration combination by RT-qPCR and ELISA methods, respectively. And the results showed that this combination inactivates the intrinsic apoptotic pathway in the PC-9 cell line.

Keywords

Lung cancer , Chemoresistance , Melissa officinalis , Osimertinib

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