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

作者：Zhang, Yonghui; Wang, Chen; Li, Jiaxin; Jin, Lishan; Ding, Wenxuan; Liu, Huan; Zhou, Na; Ren, Zhengni; Zhang, Junqi; Wei, Yong; Li, Lei; Pan, Lianhong^*; Liu, Dan^*

来源：Oncologie, 2023, 25(2): 187-197.

DOI：10.1515/oncologie-2023-0001

• growth differentiation factor 11
• JNK
• liver cancer
• ROS
• transcriptome

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.