YQFM Alleviates Side Effects Caused by Dasatinib through the ROCK/MLC Pathway in Mice.

ABSTRACT

Dasatinib, as a second-generation broad-spectrum tyrosine kinase inhibitor, presents an antitumor effect by inhibiting tyrosine kinases. However, dasatinib causes serious side effects, such as gastrointestinal bleeding and liver toxicity, possibly through the activation of ROCK kinase and MLC phosphorylation. At present, there is no effective prevention and treatment method. Previous research studies have shown that YQFM (YiQiFuMai powder injection) protects the blood-brain barrier by inhibiting the ROCK/MLC signaling pathway; whether YQFM can alleviate the side effects of dasatinib is unknown. In this study, dasatinib was injected (i.p. 70 mg/kg) and YQFM (i.p. 0.336 g/kg, 0.672 g/kg, 1.342 g/kg) was given in advance for 3 days to mice, to explore the effect of YQFM on side effects induced by Dasatinib. The results confirmed that YQFM significantly decreased Evans blue leakage in the small intestine and increased intestinal blood flow, increased the expression of ZO-1, Occludin, and VE-cadherin, and reduced the contents of D-lactic acid, s-VE-cadherin, Alanine aminotransferase (ALT), and Aspartate aminotransferase (AST) in serum. Finally, YQFM inhibited the expression of ROCK-1 and phosphorylation of MLC induced by Dasatinib. These findings suggested that YQFM could improve the side effects caused by Dasatinib linked with the ROCK/MLC signaling pathway, as shown in the graphical abstract.