Abstract

To investigate the alleviating effects of low-intensity pulsed ultrasound (LIPUS) on myelosuppression of Sprague–Dawley rats with breast cancer induced by cyclophosphamide (CTX). Breast cancer in rats was triggered by intragastric gavage with 7,12-dimethylbenz[a]anthracene (150 mg/kg). Then, the rats with breast cancer were randomly allocated to the LIPUS group (n=50) and the control group (n=50). The LIPUS group was injected intraperitoneally with CTX (50 mg/kg) for 4 consecutive days and underwent LIPUS treatment at femoral metaphysis 20 min per day from the first day of injection for 7 consecutive days. The control group was injected with CTX (50 mg/kg) and treated with LIPUS without energy output. Blood, enzyme-linked immunosorbent assay (ELISA), real-time quantitative polymerase chain reaction, Hematoxylin and Eosin (H&E) staining, and scanning electron microscopy were applied to detect the changes. The results indicated that LIPUS significantly promoted the proliferation of bone marrow nucleated cells, white blood cells (WBCs), IgA, IgG, and IgM in the peripheral blood (P<0.05) without the damage to liver and kidney function simultaneously. The mechanisms may result from the LIPUS alleviation effect on bone marrow hematopoietic function through regulating cytokines such as LIPUS can increase the expression of granulocyte colony-stimulating factor (G-CSF), stem cell factor, transforming growth factor-β, and intercellular cell adhesion molecule-1, meanwhile LIPUS will decrease the expression of interleukin-6, tumor necrosis factor-α, and vascular cell adhesion molecule-1. LIPUS has potential to be a new adjuvant therapy method in clinic for ameliorating chemotherapy-induced myelosuppression.

Highlights

  • Breast cancer is the most frequently diagnosed cancer in women worldwide and the leading cause of cancer-related deaths among women in less-developed countries [1,2]

  • Chemotherapeutic drugs were used in normal rabbits without cancer and low-intensity pulsed ultrasound (LIPUS) was used after the injection of chemotherapeutic drugs [22,23]

  • To be closer to clinical practice, in this study, chemotherapeutic drugs acted on rats with breast cancer and LIPUS was used with chemotherapeutic drugs at the same time

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Summary

Introduction

Breast cancer is the most frequently diagnosed cancer in women worldwide and the leading cause of cancer-related deaths among women in less-developed countries [1,2]. Chemotherapy is one of the main effective systemic treatments for breast cancer, in which cyclophosphamide (CTX) is widely used in the early stages [3]. During treatment of breast cancer leukopenia, and neutropenia, is the most common which is triggered by cytotoxic anticancer drugs having dose-limiting toxicity [4,5]. Severe leukopenia and neutropenia often result in treatment delay or dose reduction and discontinuation. Patients with neutrophil have more potential to be infected or have any other adverse case to make the quality of life and subsequent treatment worse [6]. Granulocyte colony-stimulating factors (G-CSFs) known as a drug used to treat neutropenia, such as filgrastim, lenograstim, and pegfilgrastim are widely used in clinical practice to reduce the risk of chemotherapy-induced neutropenia [7,8,9,10].

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