Campagna Roberto, Bacchetti Tiziana, Salvolini Eleonora, Pozzi Valentina, Molinelli Elisa, Brisigotti Valerio, Sartini Davide, Campanati Anna, Ferretti Gianna, Offidani Annamaria, Emanuelli Monica
Department of Clinical Sciences, Polytechnic University of Marche, 60126 Ancona, Italy.
Department of Life and Environmental Sciences, Polytechnic University of Marche, 60131 Ancona, Italy.
Antioxidants (Basel). 2020 Dec 7;9(12):1238. doi: 10.3390/antiox9121238.
Melanoma represents the most aggressive skin cancer, being responsible for the majority of deaths related with these neoplasms. Despite chemotherapy represents a frontline approach for management of the advanced stages of the disease, it displayed poor response rates and short-term efficacy due to melanoma cell resistance. Therefore, the discovery of molecules that can be used for effective targeted therapy of melanoma is crucial. In this study, we evaluated the impact of paraoxonase-2 (PON2) silencing on proliferation, viability, and resistance to treatment of the A375 melanoma cell line with chemotherapeutic drugs dacarbazine (DTIC) and cisplatin (CDDP). Due to the enzymes ability to counteract oxidative stress, we also evaluated the effect of enzyme knockdown on reactive oxygen species (ROS) production in cells treated with CDDP. The data reported clearly demonstrated that PON2 knockdown led to a significant reduction of cell proliferation and viability, as well as to an enhancement of A375 sensitivity to CDDP treatment. Moreover, enzyme downregulation was associated with an increase of ROS production in CDDP-treated cells. Although further analyses will be necessary to understand how PON2 could influence melanoma cell metabolism and phenotype, our results seem to suggest that the enzyme may serve as an interesting molecular target for effective melanoma treatment.
黑色素瘤是最具侵袭性的皮肤癌，导致了大多数与这些肿瘤相关的死亡。尽管化疗是治疗该疾病晚期的一线方法，但由于黑色素瘤细胞的耐药性，其反应率较低且短期疗效不佳。因此，发现可用于黑色素瘤有效靶向治疗的分子至关重要。在本研究中，我们评估了对氧磷酶-2（PON2）沉默对A375黑色素瘤细胞系增殖、活力以及对化疗药物达卡巴嗪（DTIC）和顺铂（CDDP）治疗耐药性的影响。由于该酶具有对抗氧化应激的能力，我们还评估了酶敲低对用CDDP处理的细胞中活性氧（ROS）产生的影响。报告的数据清楚地表明，PON2敲低导致细胞增殖和活力显著降低，以及A375对CDDP治疗的敏感性增强。此外，酶下调与CDDP处理的细胞中ROS产生增加有关。尽管需要进一步分析以了解PON2如何影响黑色素瘤细胞代谢和表型，但我们的结果似乎表明该酶可能是黑色素瘤有效治疗的一个有趣分子靶点。
