Abstract
Background: Breast cancer is the most common cancer in women worldwide and is the leading cause of death in women with cancer. One novel therapy used for breast cancer treatment is non-contact electric fields called electro-capacitive cancer therapy (ECCT) with intermediate frequency (100 kHz) and low intensity (18 Vpp). The objective of this study was to examine the effect of ECCT on mammary tumors growth in rats and observing the immune responses that play a role in fighting the tumor. Methods: Female SD rats were used and divided into four groups, namely control (NINT), placebo (NIT), non- therapy (INT), and therapy (IT) groups with 6 biological replicates in each group. Rats in INT and IT groups were treated with 7,12-dimethylbenz[a]anthracene for mammary tumor induction. Only rats in NIT and IT groups were exposed to ECCT individually for 10 hours per day for 21 days. The size of all tumors was measured with a digital caliper. The distributions of PCNA, ErbB2, caspase-3, CD68, CD4 and CD8-positive cells were observed with immunohistochemistry and scoring with ImageJ. Results: The growth rate of mammary tumors in IT group was significantly lower (p<0.05) than that in the INT group. The number of mitotic figures and the percentage of PCNA, caspase-3, and CD68- positive cells in IT group were significantly lower (p<0.05) than those in INT group. Conversely, the percentage of CD8-positive T cells in IT group was significantly higher (p<0.05) than that in INT group. Moreover, the CD4/CD8 ratio in IT group was decreased. Some tumor tissues were blackened and detached from the surrounding tissue, resulting in an open wound which then healed up upon exposure. Conclusions: Non-contact electric fields exposure showed inhibition on mammary tumor growth in rats while inducing CD8+ T cells that lead to tumor cells death and potentially helps wound healing.
Highlights
Breast cancer is the most common cancer among women in the world, in which 1 in 8 women in the world is at risk of developing breast cancer[1]
Mammary tumors morphology in INT and IT groups showed differences, in which mammary tumors in the INT group were generally more compact as previously reported by Pratiwi et al.[22] and appear bruised (Figure 2b) due to thrombocytopenia from the malignancy[31], whereas mammary tumors in the IT group were generally softer because they contained fluid[22] and some were blackened (Figure 2c)
In the present study, the significantly lower growth rate of rat mammary tumors in the IT group with a negative mean value of specific growth rates (SGR) compared to INT group with a positive mean value of SGR (Figure 2a) showed the inhibitory effect of non-contact electric fields of electro-capacitive cancer therapy (ECCT) against mammary tumor cells that are actively dividing in the animals, as we have previously reported wound healing and external electric fields exposure may accelerate wound healing by directing the migration of T cells[19] and fibroblast, as well as their proliferation and transdifferentiation[41,42]
Summary
Breast cancer is the most common cancer among women in the world, in which 1 in 8 women in the world is at risk of developing breast cancer[1]. The second, called systemic therapy, uses the circulatory system in the body to inhibit cancer cells growth that spread in parts of the body. This type of treatment includes chemotherapy, targeted therapy, and endocrine therapy[3]. A novel cancer therapy based on electric field exposure with intermediate frequency and low intensity called Tumor Treating Fields (TTFields) has been developed to prevent such negative effects of cancer therapy and still inhibit cancer growth. One novel therapy used for breast cancer treatment is non-contact electric fields called electro-capacitive cancer therapy (ECCT) with intermediate frequency (100 kHz) and low intensity (18 Vpp). Some tumor tissues were blackened and detached from the surrounding tissue, version 2
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