The RAS-RAF-ERK1/2 pathway is a crucial target for anticancer drug development because of the high prevalence of ERK activation in human cancers. Mitogen-activated protein kinases (MAPKs) are pivotal intracellular cascade molecules critical in all eukaryotic cells for the recognition of and response to external stimuli. RAS plays an important role with respect to cell proliferation. MDA-MB-231 is a triple-negative breast cancer (TNBC) cell line carrying a G13D KRAS mutant; hence, it is resistant to drugs. Herein, the authors evaluated a synthetic cell-penetrating peptide that binds to RAS with high affinity (termed RAS-binding peptide, RBP) for the treatment of MDA-MB-231 cancer. In this study, MDA-MB-231 cells exhibited reduced proliferation since RBP inhibited the interaction between RAS and RAF. Moreover, a decrease in RBP-treated MDA-MB-231 cell migration and invasion were observed. The expression of phosphorylatedERK1/2 and RAF-bound RAS was reduced by RBP treatment. In chicken egg xenografts, RBP inhibited tumor growth and metastatic invasion. Infiltration of immune cells was evaluated via histopathological analysis, and reduction in the level of Ki-67, a proliferation marker in human tumor cells, was evident through immunohistochemical (IHC). Taken together, the peptide RBP was suggested to be a new therapeutic target in RAS-mutated cancer.
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