Subcutaneous Ehrlich Ascites Carcinoma mice model for studying cancer-induced cardiomyopathy

Abstract

Cardiomyopathy is one of the characteristic features of cancer. In this study, we establish a suitable model to study breast cancer-induced cardiomyopathy in mice. We used Ehrlich Ascites Carcinoma cells to induce subcutaneous tumor in 129/SvJ mice and studied its effect on heart function. In Ehrlich Ascites Carcinoma bearing mice, we found significant reduction in left ventricle wall thickness, ejection fraction, and fractional shortening increase in left ventricle internal diameter. We found higher muscle atrophy, degeneration, fibrosis, expression of cell-adhesion molecules and cell death in tumor-bearing mice hearts. As observed in cancer patients, we found that mTOR, a key signalling molecule responsible for maintaining cell growth and autophagy was suppressed in this model. Tumor bearing mice hearts show increased expression and nuclear localization of TFEB and FoxO3a transcription factors, which are involved in the upregulation of muscle atrophy genes, lysosomal biogenesis genes and autophagy genes. We propose that Ehrlich Ascites Carcinoma induced tumor can be used as a model to identify potential therapeutic targets for the treatment of heart failure in patients suffering from cancer-induced cardiomyopathy. This model can also be used to test the adverse consequences of cancer chemotherapy in heart.

Toll-like receptor 2 deficiency hyperactivates the FoxO1 transcription factor and induces aging-associated cardiac dysfunction in mice

“…We measured the cardiomyocyte cross sectional area by wheat germ agglutinin (WGA) staining to identify the proportion of atrophic cells in TLR2-KO heart sections. Wheat Germ Agglutinin-Alexa Fluor 594 staining was used to visualise cardiomyocyte cell membranes, where atrophic cardiomyocytes exhibit smaller cell area (42). About 4% of cells in control hearts showed atrophic cardiomyocytes, whereas TLR2-KO heart sections exhibited significantly more number of atrophic cardiomyocytes (27%) (Fig.…”

Ameliorative effects of vitamin B17 on the kidney against Ehrlich ascites carcinoma induced renal toxicity in mice

“…Ehrlich ascites carcinoma (EAC) is undifferentiated carcinoma and is originally hyperdiploid and it is 100% malignancy as well as has high ability for transplantable, no‐regression, fast spread and shorter life period, as well as does not have tumor‐specific transplantation antigen …”

Semecarpus anacardiumLinn. leaf extract exhibits activities against breast cancer and prolongs the survival of tumor-bearing mice

“…The EAC cells are mouse derived ascetic carcinoma cells which easily accepted in mice body with high transplantable efficacy, rapid growth and confirmed malignancy. The subcutaneous injection of EAC cells, results the development of solid tumor model in mice, which is selected in this study (Ezzat et al, 2018; Mishra et al, 2018). BLEA has evaluated for anti-tumor potency using EAC induced allograft tumor mice model, which showed significant inhibition of tumor growth progression, delayed the tumor associated death and increase the survival of tumor bearing treated mice.…”

“…The harvested cells were diluted in 10 mM phosphate buffered saline (1X PBS) at a density of 5 × 10 6 _cells, and 200 μl of viable cell solution were injected into the peritoneal cavity of each recipient mouse of 21±1 g body weight and allowed to multiply. The EAC cells were withdrawn from peritoneal cavity of the donor mice after 8–10 days of inoculation and diluted in 1X PBS and centrifuged at 750 rpm (Remi R8C) for 5 minutes and the cell pellet was resuspended in sterile 10 mM PBS which was injected (100 μl at 1 × 10 7 cells/ml) in left thigh of female mice for developing solid tumor (Bhattacharjee et al, 2017; Mishra et al, 2018).…”