Modeling of clinical stages and evaluates the response to treatment in 4T1 tumor following by exposure to paclitaxel and doxorubicin -A pilot study.

Abstract

Abstract Background: The 4T1 is a mice transplantable mammary carcinoma cell line with the highly tumorigenic and invasive specification, making it suitable preclinical oncology model for triple- negative breast cancer (TNBC). The aim of this pilot study was to model the clinical stages and evaluate the response to treatment with the paclitaxel (PTX) and doxorubicin (DOX) in tumors caused by this cell line. Methods: The syngeneic tumors were developed in BALB/c female mice by 4T1 cell line. The mice were randomly distributed into three different groups, each contains four. A group of four was considered as healthy normal. Following tumor growth reached 100-300 mm3, two groups were received the maximum tolerated dose (MTD) of paclitaxel and doxorubicin, respectively. The group of sham control was injected with normal saline. The tumors and the tumor margins tissues were removed by surgery one week following chemotherapy. Angiogenesis genes and MVD were analyzed by real-time PCR and immunohistochemistry, respectively. Response to treatment was also assessed by standard methods of H&E staining. Results: TNBC tumors were confirmed by pathological staining. The volume of tumors and the angiogenesis gene expressions of VEGFR1, VEGFR2, and HIF1α were decreased in treated-tumors compared to control with p<0.05.The response to treatment to PTX was more than DOX, and the MVD was decreased in both the PTX and DOX chemotherapy groups. Conclusions: Although PTX is more effective than DOX in reducting of angiogenesis genes, both have the potential for treatment in the 4T1 mouse model.

Keywords

• Angiogenesis
• Doxorubicin
• Paclitaxel
• Response to treatment
• Triple-Negative Breast Cancer
• 4T1 tumor