Effect of hepatic stellate cell activation induced by drug-resistant colorectal cancer cells on colorectal cancer liver metastasis
10.19405/j.cnki.issn1000-1492.2026.09.016
- VernacularTitle: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
- Author:
Chang LU
1
;
Luyun YUAN
2
;
Haijing WANG
3
Author Information
1. Department of General Surgery， Putuo Hospital， Shanghai University of Traditional Chinese Medicine， Shanghai 200062
2. Department of Traditional Chinese Medicine Oncology， Putuo Hospital， Shanghai University of Traditional Chinese Medicine， Shanghai 200062
3. Department of Pharmacy， Putuo Hospital， Shanghai University of Traditional Chinese Medicine， Shanghai 200062
- Publication Type:Journal Article
- Keywords:
colorectal cancer;
drug-resistant cells;
RUNX1;
hepatic stellate cells;
liver metastasis;
tumor microenvironment
- From:
Acta Universitatis Medicinalis Anhui
2026;61(9):1634-1640
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo investigate the effect and mechanism of hepatic stellate cells （HSCs） activation induced by drug-resistant colorectal cancer cells on liver metastasis of colorectal cancer. MethodsThe expression differences of RUNX1 in colorectal cancer sensitive cells （HCT116） and drug-resistant cells （HCT116/OXA） were detected 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 migration 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. ResultsThe 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 cancer cells （P<0.05）. Following pretreatment of HCT116/OXA cells with Ro5-3335， CM derived from the corresponding HSCs significantly reduced the numbers of migrating and invading CRC cells （P<0.05）. ConclusionDrug-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.
