Influence of Paclitaxel and Doxorubicin Therapy of ßIII-Tubulin, Carbonic Anhydrase IX, and Survivin in Chemically Induced Breast Cancer in Female Rat.

Alena Pastornická,Ingrid Hodorová,Andriana Pavliuk-Karachevtseva,Slávka Drahošová,Andrea Kreheľová,Silvia Rybárová,Jozef Mihalik

doi:10.3390/ijms22126363

Abstract

Breast cancer is the most common cancer in females. The aim of this study was to determine the effect of paclitaxel (PTX) and doxorubicin (DOX) therapy on the βIII-tubulin, carbonic anhydrase IX (CA IX), and survivin expression in chemically-induced rat mammary tumors. Animals with induced mammary carcinogenesis were randomly divided into treatment groups and an untreated group. The total proportion of tumors, the proportion of carcinoma in situ (CIS), and invasive carcinoma (IC) were evaluated. Protein expression in tumor tissue was determined using IHC. Statistical analysis of the data, evaluated by Fisher-exact test and unpaired t-test. Significantly increased levels of proteins in the tumor cells were confirmed using the IHC method for all studied proteins. The expression of βIII-tubulin, CA IX, and survivin increased significantly after treatment with both cytostatics (PTX and DOX). Depending on the type of tumor, a significant increase in all proteins was observed in IC samples after PTX treatment, and CA IX expression after DOX treatment. In CIS samples, a significant increase of βIII-tubulin and survivin expression was observed after a DOX treatment. The results suggest that βIII-tubulin, survivin, and CA IX may be significant drug resistance markers and the clinical regulation of their activity may be an effective means of reversing this resistance.

Highlights

Breast cancer is the most common cancer in women today
We investigated whether levels of βIII-tubulin, carbonic anhydrase IX (CA IX), and survivin could change in induced breast cancer in rats as a result of treatment with PTX
This study demonstrates that diffuse cytoplasmic overexpression of βIII-tubulin, survivin, and CA IX in tumor tissues of mammary gland carcinoma is related to chemosensitivity

Summary

Introduction

Breast cancer is the most common cancer in women today It is the fifth leading cause of death (6.6%) and causes the highest number of deaths (approximately 15%). Related to women’s cancer [1] Anthracyclines, such as doxorubicin and epirubicin, taxanes, including paclitaxel and docetaxel, and fluorouracil and cyclophosphamide are current first-line therapeutics for the combined adjuvant treatment of breast cancer [2]. Lipid peroxidation, cell membrane damage, DNA damage, and oxidative stress occur, leading to apoptosis [2]. Resistance to these chemotherapeutics is a primary barrier to effective treatment because resistance to apoptosis is an important mechanism for tumor cells to contribute to cancer progression

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