Collectively, our data in the present work suggest that the SPTD-induced downregulation of PSMC3, SQSTM1 and COL5A1 contributes to the inhibition of the growth of A549 cells, perhaps by promoting the degradation of ubiquitinated protein kinases, e.g., ERK, MAPK and AKT, and by regulating the microenvironment of the cancer cells. Here, COL5A1 is linked to cancer.