Malign Plevral Mezotelyoma Hücre Hattinda Histon Asetil Transferaz İnhibitörü Olan Anakardik Asitin Sisplatin Cevabini Arttirici Etkisi

2013 
Objective: Various signaling pathways that play important roles in cell proliferation, translation, energy production, cytoskeleton re-organization and angiogenesis are thought to be effective during the de - velopment of malignant pleural mesothelioma (MPM). In recent years, it has been shown that epigenetic changes involving histon modifications play important roles in the development of cancer and may also lead to emergence of MPM. Currently, more effective treatment options have been investigated by combining new molecules with the classic chemotherapy agents. One of these molecules is anacardic acid (AA), which is a histone acetyl transferase (HAT) inhibitor. In our study, we aimed to determine the effects of AA and cisplatin (CDDP) combination on cMYC, NFK B, FOXO3A and BCL2L1 mRNA expression in MPM cell line (MSTO-211H: biphasic). Material and Methods: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bro - mide test was performed to determine the effect of cisplatin and AA on cell viability. RNA isolation was performed after the treatment with selected appropriate doses of the cells. cMYC, NFK B, FOXO3A and BCL2L1 mRNA expression levels were determined by quantitative real-time polymeras4e chain reaction method from isolated RNA. Results: We determined that CDDP doses higher than 10 μM were effective on MSTO-211H cells. Cell viability in the group AA+CDDP was lower than the CDDP alone group. Pretreat - ment with AA caused a significant decline in the mRNA expression levels of investigated genes compared to CDDP alone in MSTO-211H cells. Conclusion: Our data demonstrate that pretreatment with AA lead to an effective cell death response by making cells more susceptible to CDDP, a classical chemotherapeutic agent. This preclinical study emphasizes the importance of epigenetic changes in the development of MPM.
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