Key result
Low-dose radiation enhances doxorubicin antitumor efficacy while preventing doxorubicin-induced cardiotoxicity in preclinical models.
Why the study?
Low-dose radiation (LDR) may alleviate doxorubicin-induced cardiotoxicity and potentially enhance its chemotherapeutic effect, but this dual effect needed investigation.
Does low-dose radiation enhance the antitumor effect and reduce cardiotoxicity of doxorubicin in mice with breast carcinoma xenografts?
Does low-dose radiation enhance the antitumor effect and reduce cardiotoxicity of doxorubicin in mice with breast carcinoma xenografts?
Low-dose radiation prior to doxorubicin therapy may enhance antitumor efficacy while protecting against doxorubicin-induced cardiotoxicity in a preclinical model.
Answers are grounded in this paper and cite their sources.
Hypothesis-generating for LDR with DOX in tumor models; leaves open clinical translation pending human trials.
We reported that low-dose radiation (LDR) alleviated cardiotoxicity of doxorubicin (DOX) via inhibiting myocardial cell apoptosis and oxidative stress in vivo. Here, we tested whether LDR could enhance chemotherapeutic effect of DOX and alleviate myocardial injury induced by DOX by observing cell proliferation, apoptosis, and metastasis of heterotopic tumor in vivo. Mice implanted with 4T1 breast carcinoma cells were given 7.5 mg/kg DOX or 0.9% NaCl solution 72 hours after LDR (0 or 75 mGy). The histology of tumor tissue was observed by hematoxylin and eosin staining, the apoptosis was determined by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling, and the expression of Ki67, Bcl-2, Bax, cleaved caspase3, matrix metalloproteinase 2 (MMP2), MMP9, and CD34 was detected by Western blot. Expression of Ki67 and CD34 was also detected by immunohistochemistry. Results showed that cell proliferation of the breast tumor and protein expression of the metastasis-related molecules were significantly reduced and the apoptosis of tumor cells was significantly increased in the LDR + DOX-treated tumor-bearing mice. Pretreatment with LDR significantly prevented DOX-induced cardiotoxicity likely through preventing DOX-induced mitochondrial Bcl2/Bax dyshomeostasis-induced caspase-3 cleavage-dependent apoptosis. These results suggested that LDR not only enhances DOX antitumor effect but also reduces DOX cardiotoxicity, which may potentially overcome the limitation for DOX clinical usage.
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Jiang et al. (2018) studied Breast tumor xenograft and doxorubicin-induced myocardial injury. Low-dose radiation (LDR) and doxorubicin (DOX) vs. 0.9% NaCl solution or DOX alone (LDR 0 mGy) was evaluated on Tumor cell proliferation, apoptosis, metastasis, and cardiotoxicity. Pretreatment with low-dose radiation (75 mGy) significantly enhanced the antitumor effect of doxorubicin and prevented doxorubicin-induced cardiotoxicity in mice with breast tumor xenografts.
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