The inhibitory function of GDF11/BMP11 in liver cancer by inducing apoptosis and ROS-JNK pathway

Objectives The inhibitory mechanism of growth differentiation factor 11 (GDF11) on liver cancer cells is unknown. Our study applied RNA-Seq to investigate the transcriptome results of liver cancer cells after GDF11 treatment, revealing the underlying molecule mechanisms of the inhibitory roles of GDF11 on liver cancer cells. Methods First, mRNA and protein expression levels of GDF11 were detected through the Oncomine database and tissue microassay. In vitro, Smad2/3 signaling was checked using Western blot in liver cancer cell lines (MHCC97-H and HCCLM3) after GDF11 treatment. The growth effect of GDF11 on liver cancer cells was investigated by microscopic observation and the Cell Counting Kit-8 experiment. The underlying mechanisms were explored by transcriptome experiments, flow cytometry, electron microscopy, and Western blot. Results GDF11 was reduced in human malignant liver tissues and cell lines compared to normal liver tissues and cell lines. GDF11 activated Smad2/3 signaling and decreased cell viability in liver cancer cell lines (MHCC97-H and HCCLM3). RNA-Seq analysis found that 39 genes were significantly changed, 9 genes were significantly downregulated, and 30 genes were significantly upregulated. GDF11 could affect apoptosis and ROS, and JNK signaling. Conclusions GDF11 may have anti-liver cancer effects by affecting Smad2/3 and inducing apoptosis through the ROS-JNK pathway.