Ryoo Ga-Hee, Kim Geum Jin, Han Ah-Reum, Jin Chang Hyun, Lee Hunmin, Nam Joo-Won, Choi Hyukjae, Jung Chan-Hun
Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup-si, Jeollabuk-do, 56212, South Korea.
College of Pharmacy, Yeungnam University, Gyeongsan-si, Gyeongsangbuk-do, 38541, South Korea.
Heliyon. 2023 Sep 14;9(9):e20179. doi: 10.1016/j.heliyon.2023.e20179. eCollection 2023 Sep.
Lung cancer, which has a high incidence and mortality rates, often metastasizes and exhibits resistance to radiation therapy. Seongsanamide B has conformational features that suggest it has therapeutic potential; however, its antitumor activity has not yet been reported. We evaluated the possibility of seongsanamide B as a radiation therapy efficiency enhancer to suppress γ-irradiation-induced metastasis in non-small cell lung cancer. Seongsanamide B suppressed non-small cell lung cancer cell migration and invasion caused by γ-irradiation. Furthermore, it suppressed γ-irradiation-induced upregulation of Bcl-X and its downstream signaling molecules, such as superoxide dismutase 2 (SOD2) and phosphorylated Src, by blocking the nuclear translocation of phosphorylated STAT3. Additionally, seongsanamide B markedly modulated the γ-irradiation-induced upregulation of E-cadherin and vimentin. Consistent with the results obtained , while seongsanamide B did not affect xenograft tumor growth, it significantly suppressed γ-irradiation-induced metastasis by inhibiting Bcl-X/SOD2/phosphorylated-Src expression and modulating E-cadherin and vimentin expression in a mouse model. Thus, seongsanamide B may demonstrate potential applicability as a radiation therapy efficiency enhancer for lung cancer treatment.
肺癌发病率和死亡率高，常发生转移且对放射治疗产生抗性。成山酰胺B具有的构象特征表明它具有治疗潜力；然而，其抗肿瘤活性尚未见报道。我们评估了成山酰胺B作为放射治疗效率增强剂以抑制非小细胞肺癌中γ射线诱导转移的可能性。成山酰胺B抑制了γ射线诱导的非小细胞肺癌细胞迁移和侵袭。此外，它通过阻断磷酸化STAT3的核转位，抑制了γ射线诱导的Bcl-X及其下游信号分子如超氧化物歧化酶2（SOD2）和磷酸化Src的上调。此外，成山酰胺B显著调节了γ射线诱导的E-钙黏蛋白和波形蛋白的上调。与所得结果一致，虽然成山酰胺B不影响异种移植瘤生长，但在小鼠模型中它通过抑制Bcl-X/SOD2/磷酸化-Src表达并调节E-钙黏蛋白和波形蛋白表达，显著抑制了γ射线诱导的转移。因此，成山酰胺B可能作为肺癌治疗的放射治疗效率增强剂显示出潜在的适用性。
