Key result
Dasatinib, nilotinib, and sorafenib inhibit vascular smooth muscle cell proliferation and promote apoptosis in vitro.
Why the study?
Tyrosine kinase inhibitors like dasatinib, nilotinib, and sorafenib carry growing concerns for cardiotoxicity, but their impact on vascular smooth muscle cells remains unexplored.
Do dasatinib, sorafenib, and nilotinib induce inflammation, apoptosis, and inhibit proliferation and migration in vascular smooth muscle cells?
Do dasatinib, sorafenib, and nilotinib induce inflammation, apoptosis, and inhibit proliferation and migration in vascular smooth muscle cells?
p-value: p=<0.05
Dasatinib, sorafenib, and nilotinib inhibit VSMC proliferation and migration while inducing inflammatory and apoptotic pathways, providing a potential mechanism for TKI-associated vascular toxicity.
May link TKIs to vascular toxicity via VSMC effects; hypothesis-generating and requires clinical validation.
BACKGROUND: Dasatinib, nilotinib, and sorafenib are clinically proven tyrosine kinase inhibitors (TKIs) used for the treatment of leukemia and hepatocellular carcinoma. However, there is a growing concern regarding cardiotoxicity associated with their use. The impact of these TKIs on vascular smooth muscle cells (VSMCs) remains unexplored. This study aims to investigate the effects of TKIs on VSMC proliferation and migration, as well as to elucidate the underlying mechanisms involving inflammatory and apoptotic pathways. METHODS: VSMCs were extracted from albino rats and cultured in vitro. The cells were divided into four experimental groups: control, dasatinib, sorafenib, and nilotinib. The MTT assay was employed to assess the cytotoxic effects of TKIs on VSMCs. A scratch assay was conducted to evaluate the inhibitory potential of TKIs on VSMC migration. Flow cytometry analysis was used to detect apoptotic cells. Real-Time PCR expression was utilized to determine the differential gene expression of apoptotic and inflammatory markers. RESULTS: < 0.05). Furthermore, gene expression analysis revealed up-regulation of inflammatory biomarkers (TNF-α, IL-6, and IL-1β) and apoptotic markers (P53, BAX), along with down-regulation of the anti-apoptotic biomarker BCL-2 in response to all TKIs. CONCLUSIONS: This study demonstrates that dasatinib, nilotinib, and sorafenib inhibit VSMC proliferation and migration, suggesting their potential to induce vascular injury and remodeling by activating inflammation and apoptosis pathways. These findings highlight the need for further investigation into the cardiotoxic effects of these TKIs and the development of strategies to mitigate their adverse vascular effects.
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Alhazzani et al. (2023) studied Cardiotoxicity and vascular remodeling. Dasatinib, sorafenib, and nilotinib vs. Vehicle control (5% DMSO) was evaluated on Cellular viability, migration, and apoptosis of vascular smooth muscle cells (p=<0.05). Dasatinib, nilotinib, and sorafenib significantly inhibited vascular smooth muscle cell proliferation and migration while upregulating inflammatory and apoptotic markers in vitro.
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