首页|热疗与化疗联合应用抑制肝癌细胞DNA损伤修复诱导细胞凋亡的机制研究

热疗与化疗联合应用抑制肝癌细胞DNA损伤修复诱导细胞凋亡的机制研究

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在肿瘤的综合治疗中,热疗作为一种非常重要的辅助手段,在临床上可与化疗发挥协同作用,提高癌症患者的生存率,但是,其中的机制尚未完全阐明.本研究在热疗促进caspase-8 积累的基础上,结合化疗药物顺铂(CDDP),我们探索了热疗联合顺铂促进癌细胞死亡的分子机制.即最佳处理条件下联合应用诱导caspase-8的积累和激活,同时使caspase-3 的激活增加,细胞活力下降,细胞凋亡增加.进一步探讨得出CUL3 作为E3 连接酶与caspase-8 通过K63 连接泛素化积累有关.另外,我们的结果表明,联合应用诱导HepG2 细胞中DNA-PK的降解,抑制DNA-PKcs、Ku80 活性,抑制DNA修复,提高CDDP化疗效果.
The Mechanism of Apoptosis induced by Hyperthermia combined with Chemotherapy inhibiting DNA Damage Repair in Hepatocellular Carcinoma Cells
Hyperthermia can play a synergistic role with chemotherapy in clinical practice.However,the underlying mechanism has not been fully illuminated yet.In this study,we explored the molecular mechanism of hyperthermia in combination with cisplatin(CDDP)in promoting cancer cell death.Under the optimal condition,we found that combination therapy resulted in the accumulation and activation of caspase-8,which is accompanied by increased activation of caspase-3,increased cell apoptosis,and decreased cell viability.Further investigation showed that CUL3 as E3 ligase is related to the ubiquitination accumulation of caspase-8 through K63-linked.In addition,our results showed that combination therapy induced DNA-PK degradation in HepG2 cells,inhibited the activity of DNA-PKcs and Ku80,inhibited DNA repair,improved the effect of CDDP.

tumor hyperthermiacombination therapyDNA damageapoptosischemotherapy

字光慧、陈瑾、王越、彭保卫

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大理大学,云南 大理 671000

肿瘤热疗 联合应用 DNA损伤 细胞凋亡 化疗

2024

广东化工
广东省石油化工研究院

广东化工

影响因子:0.288
ISSN:1007-1865
年,卷(期):2024.51(4)
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