Department of Radiation Oncology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
Department of Radiation Oncology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
Cells. 2023 May 25;12(11):1475. doi: 10.3390/cells12111475.
5-FU-based chemoradiotherapy (CRT) and oxaliplatin-based CRT are commonly used therapies for advanced colorectal cancer (CRC). However, patients with a high expression of ERCC1 have a worse prognosis than those with a low expression. In this study, we investigated the effect of XPF-ERCC1 blockers on chemotherapy and 5-FU-based CRT and oxaliplatin (OXA)-based CRT in colorectal cancer cell lines. We investigated the half-maximal inhibitory concentration (IC) of 5-FU, OXA, XPF-ERCC1 blocker, and XPF-ERCC1 blocker, and 5-FU or OXA combined and analyzed the effect of XPF-ERCC1 blocker on 5-FU-based CRT and oxaliplatin-based CRT. Furthermore, the expression of XPF and γ-H2AX in colorectal cells was analyzed. In animal models, we combined the XPF-ERCC1 blocker with 5-FU and OXA to investigate the effects of RC and finally combined the XPF-ERCC1 blocker with 5-FU- and oxaliplatin-based CRT. In the IC analysis of each compound, the cytotoxicity of the XPF-ERCC1 blocker was lower than that of 5-FU and OXA. In addition, the XPF-ERCC1 blocker combined with 5-FU or OXA enhanced the cytotoxicity of the chemotherapy drugs in colorectal cells. Furthermore, the XPF-ERCC1 blocker also increased the cytotoxicity of 5-FU-based CRT and OXA -based CRT by inhibiting the XPF product DNA locus. In vivo, the XPF-ERCC1 blocker was confirmed to enhance the therapeutic efficacy of 5-FU, OXA, 5-FU-based CRT, and OXA CRT. These findings show that XPF-ERCC1 blockers not only increase the toxicity of chemotherapy drugs but also increase the efficacy of combined chemoradiotherapy. In the future, the XPF-ERCC1 blocker may be used to improve the efficacy of 5-FU- and oxaliplatin-based CRT.
5-FU 为基础的放化疗和奥沙利铂为基础的放化疗是治疗晚期结直肠癌（CRC）的常用方法。然而，ERCC1 高表达的患者预后比低表达的患者差。在这项研究中，我们研究了 XPF-ERCC1 抑制剂对结直肠癌细胞系化疗和 5-FU 为基础的放化疗和奥沙利铂（OXA）为基础的放化疗的影响。我们研究了 5-FU、OXA、XPF-ERCC1 抑制剂和 XPF-ERCC1 抑制剂与 5-FU 或 OXA 联合的半数最大抑制浓度（IC），并分析了 XPF-ERCC1 抑制剂对 5-FU 为基础的放化疗和奥沙利铂为基础的放化疗的影响。此外，分析了结直肠细胞中 XPF 和 γ-H2AX 的表达。在动物模型中，我们将 XPF-ERCC1 抑制剂与 5-FU 和 OXA 联合使用，研究了 RC 的效果，最后将 XPF-ERCC1 抑制剂与 5-FU 和奥沙利铂为基础的放化疗联合使用。在每种化合物的 IC 分析中，XPF-ERCC1 抑制剂的细胞毒性低于 5-FU 和 OXA。此外，XPF-ERCC1 抑制剂与 5-FU 或 OXA 联合使用增强了化疗药物在结直肠细胞中的细胞毒性。此外，XPF-ERCC1 抑制剂还通过抑制 XPF 产物 DNA 位点，增加了 5-FU 为基础的放化疗和 OXA 为基础的放化疗的细胞毒性。在体内，XPF-ERCC1 抑制剂被证实增强了 5-FU、OXA、5-FU 为基础的放化疗和 OXA 为基础的放化疗的治疗效果。这些发现表明，XPF-ERCC1 抑制剂不仅增加了化疗药物的毒性，还增加了联合放化疗的疗效。在未来，XPF-ERCC1 抑制剂可能被用于提高 5-FU 和奥沙利铂为基础的放化疗的疗效。
Zotero 插件
