Sulforaphane improves chemotherapy efficacy by targeting cancer stem cell-like properties via the miR-124/IL-6R/STAT3 axis

Gastric carcinoma (GC) is the second leading cause of cancer-related mortality worldwide. The efficacy of standard chemotherapy for GC, such as cisplatin (CDDP), is dissatisfactory partly due to the toxic/side-effects. Sulforaphane (SFN), which exhibits effective anti-cancer functions, is a phytochemical converted from cruciferous plants. Our present study aimed to identify whether SFN could enhance the anti-cancer effects of low-dose CDDP and to determine the underlying mechanisms. Herein, co-exposure of SFN and CDDP significantly inhibited the viabilities of gastric cancer cells. For the molecular mechanisms, CDDP alone increased the cancer stem cell (CSC)-like properties in gastric cancer cells via activating the interleukin-6 (IL-6)/IL-6 receptor (IL-6R)/signal transducer and activator of transcription 3 (STAT3) signaling. However, SFN could activate the microRNA-124 (miR-124), which directly targets the 3'-untranslated regions (UTR) of the IL-6R and STAT3. Moreover, knockdown of miR-124 eliminated the effects of SFN on CSC-like properties in GC cells, and in turn enhanced the anti-cancer effects of low-dose CDDP. These findings not only suggested a mechanism whereby SFN enhanced the anti-cancer functions of CDDP, but also helped to regard SFN as a potential chemotherapeutic factor in gastric cancer.