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经电离辐射修饰的 Kenalog 通过提高活性氧水平诱导黑色素瘤中的内在细胞凋亡。

Kenalog modified by ionizing radiation induces intrinsic apoptosis mediated by elevated levels of reactive oxygen species in melanoma cancer.

机构信息

Advanced Radiation Technology Institute (ARTI), Korea Atomic Energy Research Institute (KAERI), Jeongeup‑si, Jeollabuk‑do 580‑185, Republic of Korea.

出版信息

Oncol Rep. 2019 Mar;41(3):1837-1850. doi: 10.3892/or.2018.6940. Epub 2018 Dec 19.

DOI:10.3892/or.2018.6940
PMID:30569155
Abstract

Kenalog is a synthetic glucocorticoid drug used to treat various cancers including ocular and choroidal melanoma. However, the drug achieves rarely sustainable results for patients. To overcome this difficulty, the structure of Kenalog was altered by ionizing radiation (IR) to develop a more effective anticancer agent for treatment of various skin cancers. The anticancer effect of modified Kenalog (Kenalog‑IR) was assessed in melanoma cancer cells in vitro. The assessment of mitochondrial functions by MTT assay revealed significant inhibition of melanoma cancer cell viability by Kenalog‑IR compared to Kenalog. Moreover, Kenalog‑IR‑induced apoptotic cell death was associated with the intrinsic mitochondrial pathway by triggering the release of intrinsic apoptosis molecules through activation of caspase‑related molecules in concentration and time‑dependent manners. Furthermore, it was observed that Kenalog‑IR‑induced apoptosis was associated with the generation of reactive oxygen species (ROS) with increased G2/M cell cycle arrest. Collectively, Kenalog‑IR may be a potential suppressor of skin‑related cancer in particular melanoma cancer.

摘要

确炎舒松是一种合成的糖皮质激素药物,用于治疗各种癌症,包括眼和脉络膜黑色素瘤。然而,该药物对患者的疗效往往难以持久。为了克服这一困难,通过电离辐射(IR)改变 Kenalog 的结构,开发出一种更有效的抗癌药物,用于治疗各种皮肤癌。在体外评估了改良 Kenalog(Kenalog-IR)对黑色素瘤癌细胞的抗癌作用。MTT 测定评估线粒体功能的结果显示,与 Kenalog 相比,Kenalog-IR 显著抑制黑色素瘤癌细胞的活力。此外,Kenalog-IR 诱导的细胞凋亡死亡与内在的线粒体途径有关,通过激活 caspase 相关分子,以浓度和时间依赖的方式触发内在凋亡分子的释放。此外,还观察到 Kenalog-IR 诱导的细胞凋亡与活性氧(ROS)的产生有关,导致 G2/M 细胞周期停滞增加。总的来说,Kenalog-IR 可能是一种抑制皮肤相关癌症,特别是黑色素瘤的潜在药物。

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