1. Department of Nursing,Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China.
2. Department of Ultrasound, Taian Maternal and Child Health Hospital, Taian 310014, Shandong Province, China.
3. General Surgery, Cancer Center, Department of Gastrointestinal and Pancreatic Surgery, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China.
Background: Previous studies have showed that lycorine can restrain the development of multiple tumor types, containing hepatocellular carcinoma (HCC), but the underlying mechanisms remain unknown.
Methods: We assessed the impact of lycorine on hepatocellular cancer cell proliferation, migration, colony formation, cell cycle, and apoptosis. The possible inhibitory effect of lycorine on the activity of HCC cells was analyzed by RNA-seq, and transketolase (TKT) expression in HCC and nontumorous tissues was detected using RT-PCR. The expression of TKT protein in HCC and tumor adjacent non-cancerous tissues was detected by immunohistochemistry. We evaluated the association of expression of TKT in HCC tissues with prognosis, and investigated the inhibitory effect of lycorine on tumor growth in vivo.
Results: Lycorine significantly inhibited the proliferation, invasion, migration, colony formation, cell cycle of HCC cells, but had no obvious impact on apoptosis. Twenty-eight genes were found to be down-regulated in HuH7 and HepG2 cells after lycorine treatment, and the difference of TKT gene expression was significantly. The expression of TKT protein was significantly higher in HCC than in non-tumorous tissues. The expression of TKT was correlated with tumor size, Edmondson grade, AFP, and overall survival. Survival analysis suggested that high expression of TKT was associated with a poor survival. The average tumor volume and weight were significantly reduced in the lycorine injection group, but the body weights of the mice did not change significantly.
Conclusion: Lycorine can restrict the migration and proliferation of HCC cells by down-regulating TKT expression, and it may be a potential meaningful drug for the prevention and treatment of HCC.
Keywords: Lycorine, Proliferation, Migration, Hepatocellular carcinoma cells, Transketolase