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BBackground: The prominent hallmark of malignancies is the metastatic spread of cancer cells. Recent studies have reported that the nature of invasive cells could be changed after this phenomenon, causing chemotherapy resistance. It has been demonstrated that the up-regulated expression of matrix metalloproteinase (MMP) 2/MMP-9, as a metastasis biomarker, can fortify the metastatic potential of leukemia. Furthermore, investigations have confirmed the inhibitory effect of cannabinoid and endocannabinoid on the proliferation of cancer cells in vitro and in vivo. Methods: In the present study, the inhibitory effect of WIN 55212-2 a CB1/CB2 receptor agonist) and AM251 (a selective CB1 receptor antagonist) on K562 cells, as a chronic myelogenous leukemia (CML) model, was evaluated using MTT and invasion assay. Expressions of MMP-2 and MMP-9 were then assessed by Western blot analysis. Results: The data obtained from MTT assay showed that WIN 55212-2 could attenuate cell proliferation; however, AM251 was less effective in this regard. Our results showed that WIN 55212-2 considerably reduced cancer cell invasiveness, while AM251 exhibited a converse effect. Moreover, CB1 activation resulted in decreased expression of MMP-2 and MMP-9. Conclusion: Our findings clarifies that CB1 receptors are responsible for anti-invasive effects in the K562 cell line. 

Keywords: AM251, Cannabinoid receptor, Leukemia, Matrix metalloproteinases, WIN 55212-2

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