Abstract
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.
Highlights
Whether SFN could be the potent agent, which facilitated the chemotherapy efficacy of low-dose CDDP in Gastric carcinoma (GC) cells and to determine by whereby these effects occurred
Accumulating evidence suggested that chemotherapy failure might be blamed for the existence of CSCs or cancer cells with CSC-like properties, which have been identified in various types of cancer cells
Our results showed that CDDP elevated the ratios of side population (SP) and CD44+/EpCAM+ cells in a dose-dependent manner
Summary
Whether SFN could be the potent agent, which facilitated the chemotherapy efficacy of low-dose CDDP in GC cells and to determine by whereby these effects occurred. We treated human GC cell lines, MGC803 and BGC823, by different concentrations of SFN or CDDP. SFN repressed the CDDP-induced CSC-like properties in GC cells.
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