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目的 探讨结直肠癌耐药细胞诱导肝星状细胞（HSCs）活化对结直肠癌肝转移的影响及机制。方法 通过Western blot和qPCR检测结直肠癌敏感细胞（HCT116）与耐药细胞（HCT116/OXA）中RUNX1的表达差异；将2种细胞的条件培养基（CM）分别与HSCs(LX-2细胞)共培养，检测HSCs活化标志物α-平滑肌肌动蛋白（α-SMA）、Ⅰ型胶原蛋白（COL1A1）的表达及细胞形态变化；通过Transwell实验和划痕实验观察活化HSCs对结直肠癌细胞HCT116迁移和侵袭能力的影响；利用RUNX1抑制剂Ro5-3335预处理耐药细胞后，检测HSCs活化水平及HSCs活化对结直肠癌肝转移的影响。结果 Western blot和qPCR结果显示，结直肠癌耐药细胞HCT116/OXA中的RUNX1蛋白及mRNA表达水平高于敏感细胞（P<0.01）；对于LX-2细胞，CM(HCT116/OXA)组相比于CM(HCT116)组呈现出更明显的梭形样形态改变，且HSCs中α-SMA和COL1A1的表达水平更高（P<0.05,P<0.01）；与对照组相比，经活化的HSCs的CM处理后，结直肠癌细胞的迁移及侵袭细胞数增加（P<0.05）；经RUNX1抑制剂处理后，相应HSCs的CM使结直肠癌细胞迁移和侵袭的细胞数减少（P<0.05）。结论 结直肠癌耐药细胞可通过RUNX1诱导HSCs活化，进而促进结直肠癌肝转移，RUNX1可能成为结直肠癌肝转移治疗的潜在靶点。
Abstract：Objective To investigate the effect and mechanism of hepatic stellate cells(HSCs) activation induced by drug-resistant colorectal cancer cells on liver metastasis of colorectal cancer.Methods The expression differ‑ences of RUNX1 in colorectal cancer sensitive cells(HCT116) and drug-resistant cells(HCT116/OXA) were de‑tected by Western blot and qPCR. HSCs(LX-2 cells)were treated with conditioned medium(CM) derived from the two cell lines, and the expression of HSCs activation markers α-smooth muscle actin(α-SMA) and collagen type I(COL1A1) and the morphological changes of HSCs were detected. The effect of activated HSCs on the migra‑tion and invasion of colorectal cancer cells(HCT116) was observed by Transwell assay and wound healing assay. After pretreatment of drug-resistant cells with the RUNX1 inhibitor(Ro5-3335), the activation level of HSCs and its effect on liver metastasis of colorectal cancer were detected.Results The expression levels of RUNX1 protein and mRNA in the drug-resistant HCT116/OXA cells were significantly higher than those in the sensitive cells(P<0. 01). Compared with the CM(HCT116) group, the CM(HCT116/OXA) group could exhibit more pronounced spindle-shaped morphological changes, and the expression levels of α-SMA and COL1A1 in HSCs were higher(P<0. 05 and P<0. 01, respectively). Activated HSCs promoted the migration and invasion abilities of colorectal can‑cer cells(P<0. 05). Following pretreatment of HCT116/OXA cells with Ro5-3335, CM derived from the corre‑sponding HSCs significantly reduced the numbers of migrating and invading CRC cells(P<0. 05).Conclusion Drug-resistant colorectal cancer cells can induce the activation of HSCs through RUNX1 to promote liver metastasis of colorectal cancer. RUNX1 may be a potential target for the treatment of liver metastasis of colorectal cancer.
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基本信息:
DOI：10.19405/j.cnki.issn1000-1492.2026.09.016
中图分类号:R735.34
引用信息:
[1]路畅,袁路云,王海静.结直肠癌耐药细胞诱导肝星状细胞活化对肿瘤肝转移的影响[J].安徽医科大学学报,2026(09):1634-1640.DOI:10.19405/j.cnki.issn1000-1492.2026.09.016.
基金信息:
国家自然科学基金项目(编号:82505694); 上海市第六人民医院联合共建科学研究基金项目(编号:24-LY-02)
2026-08-07
2026-08-07
2026-08-07