tofacitinib and Liver-Neoplasms

Liver cancer severely threatens public health. Molecular targeted treatment is the further of cancer treatment. The functional role of Sir-related enzymes 4 (sirtuin 4) in treating liver cancer still requires further investigation. This study aimed to elucidate the effect of sirtuin 4 on aging of SMCC7721 liver cancer cell line, to underlying molecular mechanism and potential application in clinics.. Adriamycin-induced aging model was established on SMCC7721 liver cancer cell line. Sirtuin 4 over-expression or siRNA plasmid was transfected. Cell aging was measured by β-galactosidase approach. Aging-related proteins P53 and P16 were quantified in Western blot, which also examined activation of Janus kinase 2 (JAK2) signal pathway. CP-690550 was used to suppress JAK2 signal pathway for measuring aging status of SMCC7721 cells.. In aged SMCC7721 cells, sirtuin 4 was up-regulated, whilst P53 and P16 protein levels were elevated, in accompanied with JAK2/STAT3 signal pathway. Transfection of sirtuin 4 over-expression plasmid or siRNA increased or decreased sirtuin 4 expression. Adriamycin-induced aging was enhanced or suppressed, accompanied with inhibited or potentiated JAK2 signal pathway in sirtuin 4 up-regulation or down-regulation cells, respectively. The usage of JAK2 signal inhibitor, CP-690550, enhanced Adriamycin-induced cell aging.. Sirtuin 4 facilitates Adriamycin-induced aging of SMCC7721 liver cancer cells via inhibiting JAK2/STAT3 signal pathway, thus providing one novel anti-cancer strategy.

Topics: Cell Line, Tumor; Cellular Senescence; Cyclin-Dependent Kinase Inhibitor p16; Doxorubicin; Humans; Janus Kinase 2; Liver Neoplasms; Mitochondrial Proteins; Piperidines; Pyrimidines; Pyrroles; Signal Transduction; Sirtuins; STAT3 Transcription Factor; Tumor Suppressor Protein p53