The dual enrichment of response to estrogen and estrogen signaling pathway in this study implies that solasonine may intervene with candidate genes to inhibit the proliferation or drug resistance of osteosarcoma through the non-genomic effects mediated by estrogen receptor (ESR1/ESR2) or membrane-associated estrogen receptor (GPER1), which also provides some theoretical bases for the direction of the subsequent research on Solasonine to enhance the sensitivity of chemotherapy. Here, ESR1 is linked to osteosarcoma.