How to establish a 4T1 resistance model of triple-negative breast cancer induced by cisplatin? -【Animal Modeling】

  OBJECTIVE: To establish a 4T1 drug-resistant mouse model of triple-negative breast cancer with stable drug resistance, and to lay an experimental foundation for studying the mechanism of tumor drug resistance in vivo and screening of reversing drugs.

  Method: In vivo and in vitro use cisplatin (DDP) low-dose induction and cross tumorigenicity to establish a triple-negative breast cancer resistance mouse model. Cell resistance is detected by MTT method. Real-time fluorescent quantitative PCR method to analyze the differences in the expression of resistance-related genes MDR1, BCRP, MMP7 and GST-π; immunohistochemical analysis of the differences in the expression of resistance-related proteins P-gp, BCRP, and MMP7; phosphorylation Akt (phosphorylation) Akt , P-Akt) and total Akt (total Akt, t-Akt) protein expression; small animals are imaged to observe tumor growth.

  Results: MTT showed that the resistance index of the established triple-negative breast cancer resistance 4T1 mouse model was 12.84, MDR1, BCRP, MMP7, GST-π gene mRNA and P-gp resistance mice expression levels BCRP and MMP7 protein The expression level in drug tumor tissues was higher than that in non-resistant mice (P0.05). After administering the same dose of DDP to these two model mice, the sensitivity of drug-resistant mice to DDP was significantly lower than that of non-resistant mice (P\u003c0.01).

  Conclusion: First, a 4T1 mouse model of 3T-negative breast cancer resistance was established. It provides an excellent experimental animal platform for clinical personalized treatment and drug resistance reversal research of triple-negative breast cancer.