We observed that supplemental FO/Se increases the anti-tumor response of doxorubicin through multiple mechanisms: 1) inducting Sels expression and inhibiting GPR-40 mRNA; 2) suppressing receptor tyrosine kinase EGFR and FGFR; 3) decreasing PI3K/Akt/mTOR/p70S6K/4EBP1, Raf/MEK/ERK1/2, and JAK/c-Src/STAT3 signaling; 4) activating tumor suppressor proteins PTEN, TSC1/2, and P53; 5) inhibiting nuclear oncoprotein transcriptional factors; and 6) regulating PD-1/PD-L1/CTLA-4 signaling. Here, MAPK3 is linked to neoplasm.