Carbamazepine Inhibits Lung Cancer Metastasis by Suppressing Chemokine Receptor 4 Expression.

Background: Lung cancer is one of the leading causes of cancer-related deaths worldwide, with treatment failure resulting from metastasis. C-X-C chemokine receptor type 4 ( CXCR4 ) plays a crucial role in tumor cell migration and metastasis. Recent studies have suggested that the commonly used antiepileptic drug, carbamazepine (CBZ), may impede tumor metastasis; however, its specific mechanism remains unclear.
Methods: In this study, we evaluated the effects of CBZ on the migration and invasion of lung cancer cells through in vitro cell cultures and in vivo animal models. The regulatory effect of CBZ on CXCR4 expression was analyzed using western blot and reverse transcription-quantitative polymerase chain reaction techniques. To further validate whether CBZ's anti-metastatic effect is mediated through CXCR4 , we used the CXCR4 agonist NUCC-390 and overexpression of the CXCR4 gene in lung cancer cell lines.
Results: The results demonstrated that CBZ significantly inhibited the migration and invasion of lung cancer cells (* p < 0.001). In animal experiments, CBZ treatment significantly reduced the extent of metastasis in the lungs (* p < 0.01). Moreover, CBZ downregulated the expression of CXCR4 (* p < 0.001). When NUCC-390 was used or CXCR4 was overexpressed, the anticancer effect of CBZ was reversed, indicating the anti-metastatic effect of CBZ is closely associated with its inhibition of CXCR4 expression.
Conclusion: This study reveals, for the first time, a novel mechanism by which CBZ inhibits lung cancer metastasis through the suppression of CXCR4 expression. These findings offer a new avenue for the treatment of lung cancer using CBZ as a potential agent against lung cancer metastasis. Further research is warranted to explore the clinical potential of CBZ and to offer more treatment options for lung cancer patients.