热化疗药物对人胃癌细胞毒性、化疗耐药相关蛋白和 PD-L1 表达的影响

IF 3 3区 医学 Q2 ONCOLOGY
International Journal of Hyperthermia Pub Date : 2024-01-01 Epub Date: 2024-02-13 DOI:10.1080/02656736.2024.2310017
Bor-Chyuan Su, Guan-Yu Chen, Chun-Ming Yang, Wei-Ting Chuang, Meng-Chieh Lin, Pei-Ling Hsu, Chu-Wan Lee, Chih-Cheng Cheng, Shih-Ying Wu, Bo-Syong Pan, Hsin-Hsien Yu
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引用次数: 0

摘要

目的:伴有腹膜转移的胃癌被认为是晚期胃癌。目前治疗这种情况的一种方法是联合细胞还原手术和腹腔热化疗(HIPEC)。然而,HIPEC 的治疗机制在很大程度上仍未得到阐明。方法:为了评估HIPEC在体外对细胞的影响,我们在37 °C或43 °C(高热温度)下用或不用5-氟尿嘧啶(5-Fu)处理AGS人胃腺癌细胞1小时,然后在37 °C下培养23小时,测量高热/5-Fu对细胞凋亡、细胞存活信号、氧化应激、化疗耐药相关蛋白和程序性死亡配体1(PD-L1)表达的影响。结果显示结果表明,热疗能增强 5-Fu 介导的 AGS 细胞毒性。此外,5-Fu 和热疗联合使用可降低磷酸化 STAT3 和 STAT3 的水平,同时提高磷酸化 Akt 和 ERK 的水平。此外,5-Fu/热疗还会增强活性氧并抑制超氧化物歧化酶1。化疗耐药性相关蛋白,如多药耐药性 1 和胸苷酸合成酶,也受到 5-Fu/hyperthermia 的抑制。有趣的是,热疗可增强 5-Fu 介导的糖基化 PD-L1 诱导,但热疗可阻止 5-Fu 介导的 PD-L1 表面表达上调。结论综上所述,我们的研究结果有助于开发新型治疗策略和提高 HIPEC 的疗效。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Impacts of hyperthermic chemotherapeutic agent on cytotoxicity, chemoresistance-related proteins and PD-L1 expression in human gastric cancer cells.

Objective: Gastric cancer with peritoneal metastasis is considered to be final stage gastric cancer. One current treatment approach for this condition is combined cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC). However, the therapeutic mechanisms of HIPEC remain largely undescribed. Method: In order to assess the cellular effects of HIPEC in vitro, we treated AGS human gastric adenocarcinoma cells with or without 5-fluorouracil (5-Fu) at 37 °C or at 43 °C (hyperthermic temperature) for 1 h followed by incubation at 37 °C for 23 h. The impacts of hyperthermia/5-Fu on apoptosis, cell survival signals, oxidative stress, chemoresistance-related proteins and programmed death-ligand 1 (PD-L1) expression were measured. Results: Our results showed that hyperthermia potentiates 5-Fu-mediated cytotoxicity in AGS cells. Furthermore, the combination of 5-Fu and hyperthermia reduces levels of both phosphorylated STAT3 and STAT3, while increasing the levels of phosphorylated Akt and ERK. In addition, 5-Fu/hyperthermia enhances reactive oxygen species and suppresses superoxide dismutase 1. Chemoresistance-related proteins, such as multidrug resistance 1 and thymidylate synthase, are also suppressed by 5-Fu/hyperthermia. Interestingly, hyperthermia enhances 5-Fu-mediated induction of glycosylated PD-L1, but 5-Fu-mediated upregulation of PD-L1 surface expression is prevented by hyperthermia. Conclusion: Taken together, our findings provide insights that may aid in the development of novel therapeutic strategies and enhanced therapeutic efficacy of HIPEC.

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来源期刊
CiteScore
5.90
自引率
12.90%
发文量
153
审稿时长
6-12 weeks
期刊介绍: The International Journal of Hyperthermia
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