Bai Mingjun, Zeng Zhaolin, Li Li, Wu Qiong, Zhang Yanyang, Pan Tao, Mu Luwen, Zhu Duo, Guan Shouhai, Xie Qiang, Mei Wenjie
Department of Vascular Interventional Radiology, The Third Affiliated Hospital, Sun Yat-sen University 600 Tianhe Road Guangzhou Guangdong China 510630
School of Pharmacy, Guangdong Pharmaceutical University Guangzhou China 510006
RSC Adv. 2018 Jun 6;8(37):20612-20618. doi: 10.1039/c8ra03383h. eCollection 2018 Jun 5.
A chiral ruthenium(ii) complex, Λ-[Ru(bpy)(-tFMPIP)] (ClO) (-tFMPIP = 2'-trifluoromethylphenyl) imidazo [4,5-][1,10]phenanthroline, was prepared and evaluated for its enhancement of the radiosensitivity of I seeds. The synthetic Ru(ii) complex, LR042, effectively enhanced growth inhibition against HepG2 human hepatocellular liver carcinoma cells induced by I seeds and consequently effectively promoted the apoptosis of tumor cells with increasing level of cleave-caspase-3. Furthermore, the results of immunofluorescence indicated that LR042 enhanced the phosphorylation of H2AX by I seeds vigorously in response to damaged DNA. LR042 improved DNA damage induced by I seeds, which resulted in apoptosis through the activation of the p53/AKT signal. In conclusion, synthetic LR042 can be further developed as a potential radiosensitizer of I seed radiotherapy for cancer therapy.
制备了一种手性钌（II）配合物，即Λ-[Ru(bpy)(-tFMPIP)] (ClO)（-tFMPIP = 2'-三氟甲基苯基）咪唑并[4,5-][1,10]菲咯啉，并评估了其对碘种子放射敏感性的增强作用。合成的钌（II）配合物LR042有效增强了碘种子对HepG2人肝癌细胞的生长抑制作用，并因此随着裂解型半胱天冬酶-3水平的升高有效促进了肿瘤细胞的凋亡。此外，免疫荧光结果表明，LR042能有力地增强碘种子对受损DNA的响应，使H2AX磷酸化。LR042改善了碘种子诱导的DNA损伤，通过激活p53/AKT信号导致细胞凋亡。总之，合成的LR042可进一步开发成为用于癌症治疗的碘种子放射治疗的潜在放射增敏剂。
