Wu Pei-Yi, Hasanah Ulfah, Yang Sheng-Hua, Chen Sin-Yi, Luo Yueh-Hsia, Chen Chien-Chin, Chen Ssu-Ching
Department of Life Sciences, National Central University, Taoyuan, Taiwan.
Department of Chemical Engineering, National Tsing Hua University, Hsinchu, Taiwan.
Chem Biol Interact. 2025 Jan 5;405:111291. doi: 10.1016/j.cbi.2024.111291. Epub 2024 Oct 25.
Cisplatin (cDDP) is a crucial chemotherapy drug for treating various cancers, including hepatocellular carcinoma (HCC). However, its effectiveness is often hindered by side effects and drug resistance. Selenocystine (SeC) demonstrates potential as an anticancer agent, particularly by inhibiting DNA repair mechanisms. This study explored the synergistic potential of SeC combined with cDDP for treating HCC. Our results show that SeC pretreatment followed by cDDP significantly suppresses HCC cell proliferation more effectively than either treatment alone, with minimal toxicity to normal liver cells. The combination induces significant DNA damage by inhibiting homologous recombination (HR) and non-homologous end joining (NHEJ) pathways. Xenograft experiments confirmed that the combined therapy strongly inhibits tumor growth. SeC boost the effectiveness of cDDP by amplifying DNA damage and inhibiting DNA repair, presenting a promising approach to enhancing liver cancer treatment.
顺铂（cDDP）是治疗包括肝细胞癌（HCC）在内的多种癌症的关键化疗药物。然而，其疗效常常受到副作用和耐药性的阻碍。硒代胱氨酸（SeC）显示出作为抗癌剂的潜力，特别是通过抑制DNA修复机制。本研究探讨了SeC与cDDP联合治疗HCC的协同潜力。我们的结果表明，SeC预处理后再使用cDDP比单独使用任何一种治疗方法都能更有效地显著抑制HCC细胞增殖，对正常肝细胞的毒性最小。这种联合通过抑制同源重组（HR）和非同源末端连接（NHEJ）途径诱导显著的DNA损伤。异种移植实验证实，联合治疗强烈抑制肿瘤生长。SeC通过放大DNA损伤和抑制DNA修复来提高cDDP的疗效，为增强肝癌治疗提供了一种有前景的方法。
