Response to Treatment in 4T1 Tumor Following Exposure to Paclitaxel and Doxorubicin Based on Antiangiogenic Effects

Abstract

Background: 4T1 is a mice transplantable mammary carcinoma cell line with highly tumorigenic and invasive properties, making it a suitable preclinical oncology model for triple-negative breast cancer (TNBC). This pilot study aimed to create a model of clinical stages in TNBC mice and to evaluate the response to treatment with paclitaxel (PTX) and doxorubicin (DOX) based on antiangiogenic effects. Methods: Syngeneic tumors were developed in BALB/c female mice by 4T1 cell line. The mice were randomly distributed into three different groups, each containing four. A group of four was considered as healthy normal. When tumor growth reached 100- 200 mm3 , two groups received the maximum tolerated dose (MTD) of PTX and DOX, respectively. Normal saline was injected into the sham control group. The tumors and tissue margins were removed by surgery one week following chemotherapy. Angiogenesis genes and microvessel density (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 decreased in treated tumors compared to control (p < 0.05). Response to treatment to PTX was more than DOX, and the MVD decreased in both PTX and DOX chemotherapy groups. Conclusion: Although PTX is more effective than DOX in reducing angiogenesis genes, both have the potential for treatment in the 4T1 mouse model.