Amelioration of cyclophosphamide-induced myelosuppression during treatment to rats with breast cancer through low-intensity pulsed ultrasound

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.

Low-intensity pulsed ultrasound activated the anti-tumor immunity by irradiating the spleen of mice in 4 T-1 breast cancer

“…Our results indicating that LIPUS had immune activation function in normal mice; however, we found no significant infiltration of activated CD8 + T cells in the tumor microenvironment. In contrast, in our previous study, immunoglobulin (Ig) levels were significantly elevated after LIPUS irradiation in a damaged body such as the cyclophosphamide-induced myelosuppression model in rats with breast cancer [ 17 ]. So, we hypothesized that it is possible that normal mice have a limited capacity to respond to LIPUS immune activation.…”

“…In our preliminary study, LIPUS can treat cyclophosphamide-induced leukopenia in rabbits and significantly increase serum immunoglobulin (Ig) levels in rabbits [ 16 ]. In addition, LIPUS is effective on improving serum Ig levels and enhancing the immunity of the body after cyclophosphamide chemotherapy in a rat model of breast cancer [ 17 ].…”

Sciadonic acid ameliorates cyclophosphamide‐induced immunosuppression by modulating the immune response and altering the gut microbiota

“…Cyclophosphamide (Cy), an alkylating compound, is commonly used to treat different cancers and autoimmune diseases. 2 However, long-term treatment with Cy can impair immune function, as well as the gastrointestinal mucosal barrier, causing immunosuppression, oxidative stress and various side effects. 3 In view of this, experiments are frequently performed using intraperitoneal Cy injections to establish immunosuppression models.…”

“…Chemotherapy is extensively used for treating cancer. Cyclophosphamide (Cy), an alkylating compound, is commonly used to treat different cancers and autoimmune diseases 2 . However, long‐term treatment with Cy can impair immune function, as well as the gastrointestinal mucosal barrier, causing immunosuppression, oxidative stress and various side effects 3 .…”