Establishment of a cisplatin-resistant mouse model of 4T1 triple negative breast cancer
10.3969/j.issn.1005-4847.2015.05.005
- VernacularTitle:顺铂诱导三阴性乳腺癌4T1耐药小鼠模型的建立
- Author:
Jiayu SHENG
;
Hongfeng CHEN
- Publication Type:Journal Article
- Keywords:
Triple negative breast cancer;
Neoplasm drug resistance;
Cisplatin;
Animal models;
Mice
- From:
Acta Laboratorium Animalis Scientia Sinica
2015;23(5):466-473
- CountryChina
- Language:Chinese
-
Abstract:
Objective To establish a cisplatin-resistant 4T1 mouse model of triple negative breast cancer .Meth-ods A drug resistant mice model was established with cisplatin ( DDP ) induction and in-vivo/in-vitro tumorigenic ap-proach.Its resistance characteristics were identified by MTT assay .Changes of drug resistance gene ( MDR1, BCRP, MMP7, GST-π) and protein ( P-gp, BCRP, MMP7) expression, and phosphorate-Akt and total-Akt protein expression were evaluated by real-time PCR, immunohistochemistry and western blot method , respectively.Small animal live imaging technology was applied to detect tumor growth .Results Resistance fold (RF) of cisplatin-resistant 4T1 mouse model was 12.84.The expression of MDR1, BCRP, MMP 7, GST-πmRNA and P-gp, BCRP, MMP 7 proteins in the resistant mice were higher than that in the non-resistant mice .The result of western blot showed that a statistically higher expression of p-Akt in resistant mice than that in non-resistant mice at protein levels (P<0.01).No significant difference of tumor growth rate was observed between non-resistant and resistant mice ( P>0.05 ) .Given same dose of DDP , resistant mice showed lower sensitivity than non-resistant mice significantly (P<0.01).Conclusions We have successfully established a cis-platin-resistant triple negative breast cancer model in mice , which provides a new platform for further study on chemoresis-tant reversal strategy and individualized clinical treatment of this disease .
