Kamm Anna, Przychodzeń Paulina, Kuban-Jankowska Alicja, Marino Gammazza Antonella, Cappello Francesco, Daca Agnieszka, Żmijewski Michał A, Woźniak Michał, Górska-Ponikowska Magdalena
Department of Medical Chemistry, Medical University of Gdansk, Gdansk 80-211, Poland.
Euro-Mediterranean Institute of Science and Technology, Palermo, Italy.
J Oncol. 2019 Oct 2;2019:9293416. doi: 10.1155/2019/9293416. eCollection 2019.
Melanoma is an aggressive type of skin cancer with one of the highest mortality rates. Notably, its incidence in the last few decades has increased faster than any other cancer. Therefore, searching for novel anticancer therapies is of great clinical importance. In the present study, we investigated the anticancer potential of 2-methoxyestradiol, potent chemotherapeutic, in the A375 melanoma cellular model. In order to furthermore evaluate the anticancer efficacy of 2-methoxyestradiol, we have additionally combined the treatment with a naturally occurring polyphenol, ferulic acid. The results were obtained using the melanoma A375 cellular model. In the study, we used MTT assay, flow cytometry, and western blot techniques. Herein, we have evidenced that the molecular mechanism of action of 2-methoxyestradiol and ferulic acid is partly related to the reduction of Hsp60 and Hsp90 levels and the induction of nitric oxide in the A375 melanoma cell model, while no changes were observed in Hsp70 expression after 2-methoxyestradiol and ferulic acid treatment separately or in combination. This is especially important in case of chemoresistance mechanisms because the accumulation of Hsp70 reduces induction of cancer cell death, thus decreasing antitumour efficacy.
黑色素瘤是一种侵袭性皮肤癌，死亡率极高。值得注意的是，在过去几十年中，其发病率的增长速度超过了任何其他癌症。因此，寻找新的抗癌疗法具有重要的临床意义。在本研究中，我们在A375黑色素瘤细胞模型中研究了强效化疗药物2-甲氧基雌二醇的抗癌潜力。为了进一步评估2-甲氧基雌二醇的抗癌效果，我们还将其与天然存在的多酚阿魏酸联合使用。研究结果来自黑色素瘤A375细胞模型。在该研究中，我们使用了MTT法、流式细胞术和蛋白质印迹技术。在此，我们证明了在A375黑色素瘤细胞模型中，2-甲氧基雌二醇和阿魏酸的分子作用机制部分与Hsp60和Hsp90水平的降低以及一氧化氮的诱导有关，而单独或联合使用2-甲氧基雌二醇和阿魏酸处理后，Hsp70的表达未观察到变化。这在化疗耐药机制方面尤为重要，因为Hsp70的积累会减少癌细胞死亡的诱导，从而降低抗肿瘤疗效。
