Abstract
We aimed to evaluate the cardioprotective effect and mechanism of propofol in anthracycline-induced cardiomyocyte apoptosis. We selected the rat myocardial cell line, H9c2, and primary cardiomyocytes for in vitro study. The cardiomyocytes were treated with vehicle, Adriamycin® (ADM), propofol, or a combination of ADM and propofol. The proportion of apoptotic cells and the expression of miR-181a were detected by flow cytometry and real-time PCR, respectively. Luciferase assays were performed to explore the direct target gene of miR-181a. In vivo assay, rats were randomly divided into different treatment groups. The apoptosis index was determined by TUNEL staining, and the expression of miR-181a and STAT3 in heart tissue was detected. The antiproliferative effect of ADM alone was significantly greater than that of ADM plus propofol. A significantly greater decrease in the proportion of apoptotic cells and in miR-181a expression was observed in the combination treatment group compared with that in the ADM groups in vitro and in vivo. The loss-of-function of miR-181a in H9c2 of ADM treatment resulted in increased Bcl-2 and decreased Bax. MiR-181a suppressed Bcl-2 expression through direct targeting of the Bcl-2 transcript. Propofol reduced anthracycline-induced apoptosis in cardiomyocytes via targeting miR-181a/Bcl-2, and a negative correlation between miR-181a and Bcl-2 was observed.
Highlights
The use of anthracycline (ANT) for the chemotherapy of various malignancies has been hampered by their cardiac toxicity
The results showed that the proportion of apoptotic cells was significantly elevated to 17.6% ± 0.89% in ADM-treated cells compared with 0.87% ± 0.37% in the controls (P < 0 001) but was stably maintained at 13.6% ± 0.70% upon propofol treatment
The results of this study revealed that propofol provided cardioprotective effects against ANT-induced cardiotoxicity, which were mediated by miR-181a both in vitro and in vivo
Summary
The use of anthracycline (ANT) for the chemotherapy of various malignancies has been hampered by their cardiac toxicity. The most severe is the chronic forms of cardiotoxicity, characterized by irreversible cardiac damage and congestive heart failure, which remain a major problem 50 years after the discovery of daunorubicin and doxorubicin (DOX), known as Adriamycin (ADM), and their introduction in clinics [1]. The pathophysiology of ANT-induced cardiotoxicity is still not fully understood; it remains a subject of debate and considerable controversy. Several scientists suggested that ANT-induced cardiotoxicity and myocardial dysfunction were associated with cardiomyocyte apoptosis [2,3,4]. Our previous study indicated that anthracycline could induce the apoptosis of cardiomyocytes in rats. Oxidative Medicine and Cellular Longevity we focused on the interpretation of the mechanism of anthracycline-induced apoptosis in cardiomyocytes in the presence or absence of propofol
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