KD-025(Nanjing Kaedi Biotechnology Co Ltd)

Rho-associated coiled-coil kinase (ROCK) inhibition decreases tumourogenic growth, proliferation and angiogenesis. Multifaceted evidences are there about the role of ROCK in cancer progression, but isoform specific analysis in secondary pulmonary melanoma is still unaddressed. This study explored the operating function of ROCK in the metastasis of B16F10 mice melanoma cell line. Inhibition by KD-025 indicated dual wielding role of ROCKII as it is associated with the regulation of MMP9 activity responsible for extra-cellular matrix (ECM) degradation as well as angiogenic invasion as an effect of Src-FAK-STAT3 interaction dependent VEGF switching. We found the assisting role of ROCKII, not ROCKI in nuclear localization of Smads that effectively increased MMP9 expression and activity (p < 0.01). This cleaved the protein components of ECM thereby played a crucial role in tissue remodeling at secondary site during establishment of metastatic tumour. ROCKII phosphorylation at Ser¹³⁶⁶ as an activation of the same was imprinted essential for oncogenic molecular bagatelle leading to histo-architectural change of pulmonary tissue with extracellular matrix degradation as a consequence of invasion. Direct correlation of pROCKIISer¹³⁶⁶ with MMP9 as well as VEGF expression in vivo studies cue to demonstrate the importance of pROCKIISer¹³⁶⁶ inhibition in the context of angiogenesis, and metastasis suggesting ROCKII signaling as a possible target for the treatment of secondary lung cancer specially in metastatic melanoma.