Lung cancer is a common cancer with high mortality worldwide, and non-small cell lung cancer (NSCLC) accounts for the majority. The clinical treatment effect of NSCLC is not ideal. The aim of this study was to investigate the inhibitory effect of sea cucumber peptide (SCP) on NSCLC and its mechanism. The results showed that SCP could effectively inhibit the proliferation, migration and invasion of A549 cells. In addition, SCP can also inhibit the formation of pleural effusion and tumor growth in lung cancer mice, reduce liver and kidney injury, increase the levels of IL-2 and IL-12, decrease the levels of IL-6 and TNF-α, and prolong the survival time of mice. The microRNA sequencing and immunohistochemistry of mouse tumors showed that the tumor suppressor gene TUSC2 targeted by miR-378a-5p was involved in the inhibition of tumor growth by SCP. This study provides an experimental basis for the further development of SCP as an anti-tumor nutritional supplement, and provides a new idea for exploring the molecular mechanism of food derived active peptides in anti-tumor applications.
