Research of the interaction between Wnt/β-catenin signaling and the EMT pathway in mediating sunitinib-resistance in renal cancer cells
10.13699/j.cnki.1001-6821.2024.17.006
- VernacularTitle:Wnt/β-catenin信号通路与EMT途径相互作用介导肾癌舒尼替尼耐药的研究
- Author:
Fang-Zhen CAI
1
;
Yan-Mei ZHANG
;
Si-Huai HUANG
;
Wen-Bin LIU
;
Wei-Feng ZHUO
;
Jian-Wei LI
Author Information
1. 福建医科大学附属第二医院泌尿外科,福建泉州 362000
- Keywords:
sunitinib;
Wnt/β-catenin;
epithelial mesenchymal transition;
drug resistance;
renal carcinoma
- From:
The Chinese Journal of Clinical Pharmacology
2024;40(17):2483-2487
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the mechanism of the interaction between Wnt/β-catenin signaling and the epithelial mesenchymal transition(EMT)pathway in mediating sunitinib-resistance in renal cancer cells.Methods The sunitinib-resistant kidney cancer cell lines were constructed by stepwise increase in drug concentrations method with sunitinib,and were divided into resistance group,lv-NC group and lv-Twist group,and human kidney cancer cell lines were selected as normal group.The normal and drug-resistant groups were treated with conventional culture;the lv-NC group was treated with 40 μL of lv-NC lentivirus supernatant containing 2.25 × 108 TU·mL-1 for 72 h,and the lv-Twist group was treated with 50 μL of Twist lentivirus supernatant containing 1.64 × 108 TU·mL-1 for 72 h.The apoptosis ability was detected by flow cytometry;the cell migration ability was detected by cell scratch assay;the cell invasion ability was detected by Transwell assay;and the protein expression levels of Wnt1,β-catenin and Twist were detected by Western blotting assay.Results The apoptosis rates of control,resistant,lv-NC and lv-Twist groups were(17.60±0.59)％,(8.61±0.34)％,(8.60±0.40)％and(3.10±0.34)％;the migration rates were(14.10±0.12)％,(27.64±0.41)％,(14.24±0.45)％and(32.74±2.53)％;the number of invading cells was 27.33±1.15,53.33±1.53,46.00±2.65 and 99.33±2.52;the relative expression levels of Wnt1 protein were 0.10±0.01,0.96±0.06,0.39±0.03 and 3.09±0.31;the relative expression levels of β-catenin protein were 0.39±0.01,1.48±0.16,0.81±0.05 and 1.24±0.14;the relative expression levels of Twist protein were 0.10±0.02,0.91±0.04,0.39±0.03 and 3.09±0.31,respectively.The differences of above indexes were statistically significant between the resistant group and the normal group,and between the lv-Twist group and the lv-NC group(all P＜0.05).Conclusion Twist(EMT related protein)mediates sunitinib resistance in renal cell carcinoma by interacting with Wnt/β-catenin signaling pathway.
