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

Zahra Valizadeh; Masoomeh Beheshti; Fatemeh Ashrafi; Soyar Sari; Raheleh Kheirbakhsh; Hadiseh Mohammadpour; Samad mohammadnejad; Ahad mohammadnejad; Saeid Amanpour; Marveh Rahmati

doi:10.18502/bccr.v13i2.10031

Zahra Valizadeh Cancer Biology Research Center, Cancer Institute, Tehran University of Medical Sciences, Tehran, Iran
Masoomeh Beheshti Cancer Biology Research Center, Cancer Institute, Tehran University of Medical Sciences, Tehran, Iran
Fatemeh Ashrafi Department of Cellular and Molecular Biology, Faculty of Biological Sciences, North Tehran Branch, Islamic Azad University, Tehran, Iran
Soyar Sari Department of Molecular and Cellular Sciences, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
Raheleh Kheirbakhsh Cancer Biology Research Center, Cancer Institute, Tehran University of Medical Sciences, Tehran, Iran
Hadiseh Mohammadpour Dental Research Center, Dentistry Research Institute, Tehran University of Medical Sciences, Tehran, Iran
Samad mohammadnejad Cell-Based Therapies Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
Ahad mohammadnejad Cancer Biology Research Center, Cancer Institute, Tehran University of Medical Sciences, Tehran, Iran
Saeid Amanpour Cancer Biology Research Center, Cancer Institute, Tehran University of Medical Sciences, Tehran, Iran
Marveh Rahmati Cancer Biology Research Center, Cancer Institute, Tehran University of Medical Sciences, Tehran, Iran

DOI: https://doi.org/10.18502/bccr.v13i2.10031

Keywords: Angiogenesis, Doxorubicin, Paclitaxel, Response to treatment, Triple-Negative Breast Cancer, 4T1 Tumor

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.