【Animal Modeling】-4T1 Resistant Mouse Model

  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, low-dose cisplatin (DDP) is used to induce and cross-tumor formation to establish a triple-negative breast cancer resistance mouse model. Cell resistance is detected by MTT method. Real-time fluorescent quantitative PCR method. Analysis of differences in the expression of resistance-related genes MDR1, BCRP, MMP7 and GST-π; immunohistochemical analysis of differences in the expression of resistance-related proteins P-gp, BCRP, MMP7; phosphorylated Akt (phosphorylated Akt, p-Akt) Western blot analysis) and total Akt (total Akt, t-Akt) protein expression; small animal imaging to observe tumor growth.

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