Objective To investigate the inhibitory effect of cordycepin on immune function injury in lung cancer rats after radiation therapy through JAK2/STAT3 signaling pathway. Methods Fifty rats were used to establish tumor-bearing model and other 10 rats were taken as normal group. After successful modeling, the rats were randomly divided into model group, radiotherapy group, cordycepin group, agonist group and agonist+cordycepin group (10 rats in each group). We compared tumor weight, tumor volume, tumor inhibition rate, IL-6, TNF-α, spleen index and thymus index, the number of T lymphocyte subsets, JAK2, p-JAK2, STAT3 and p-STAT3 protein expression levels among all groups. Results Compared with normal group, IL-6, TNF-α, CD8+, p-JAK2 and p-STAT3 in model group were increased, while spleen index, thymus index, CD4+ and CD4+/CD8+ were decreased (P < 0.05). Compared with model group, tumor weight, tumor volume, spleen index, thymus index, CD4+ and CD4+/CD8+ were decreased in radiotherapy group, while IL-6, TNF-α, CD8+, p-JAK2 and p-STAT3 were increased (P < 0.05). Compared with radiotherapy group, tumor weight, tumor volume, IL-6, TNF-α, CD8+, p-JAK2 and p-STAT3 were decreased in cordycepin group, while tumor inhibition rate, spleen index thymus index, CD4+ and CD4+/CD8+ were increased; tumor weight, tumor volume, IL-6, TNF-α, CD8+, p-JAK2 and p-STAT3 protein expression were increased in agonist group, while tumor inhibition rate, spleen index, thymus index, CD4+ and CD4+/CD8+ were decreased (P < 0.05). Compared with agonist+cordycepin group, tumor weight, tumor volume, IL-6, TNF-α, CD8+, p-JAK2 and p-STAT3 were decreased in cordycepin group, while tumor inhibition rate, spleen index, thymus index, CD4+ and CD4+/CD8+ were increased; tumor weight, tumor volume, IL-6, TNF-α, CD8+, p-JAK2 and p-STAT3 were increased in agonist group, while tumor inhibition rate, spleen index, thymus index, CD4+ and CD4+/CD8+ were decreased (P < 0.05). Conclusion Cordycepin can effectively inhibit the immune function injury in lung cancer rats after radiation therapy, and may play a regulatory role by inhibiting the JAK2/STAT3 signal pathway.

Objective To investigate the effect of CC chemokine receptor 4(CCR4) on sorafenib radiosensitivity and tumorigenesis of hepatocellular carcinoma cells in nude mouse models.Methods Western blot was used to detect the expression of CCR4 in hepatocellular carcinoma cell line.Lentivirus was utilized to construct PLC/PRF/5 and SMMC-7721 cell lines stably overexpressing and silencing CCR4,which were verified by Western blot.The influence of CCR4 on the radiosensitivity of hepatocellular carcinoma cells was assessed by plate clone formation assay.The effect of CCR4 on the tumorigenesis in hepatocellular carcinoma cells in vivo was evaluated by tumorigenesis assay in nude mice.Results CCR4 was highly expressed in highly-metastatic hepatocellular carcinoma cells and lowly expressed in hepatocellular carcinoma cells with low metastases.The PLC/PRF/5 and SMMC-7721 cells,which stably overexpressed and silenced CCR4,were successfully established.Overexpression of CCR4 reversed the inhibitory effect of sorafenib radiotherapy on PLC/PEF/5,whereas knockdown of CCR4 could increase the radiosensitivity of SMMC-7721 to sorafenib.Overexpressing CCR4 could promote the tumorigenicity of PLC/PEF/5,whereas knockdown of CCR4 could inhibit the tumorigenicity of SMMC-7721 in nude mice.Conclusion CCR4 overexpression significantly reduces the radiosensitivity of PLC/PRF/5 and increases the tumorigenicity in nude mice,whereas knockdown of CCR4 considerably increases the chemosensitivity and radiosensitivity of SMMC-7721 and suppresses the tumorigenicity in nude mice.

Objective: To investigate the effect of silencing GRAMD1A and inhibiting STAT5 signaling pathway on the radiosensitivity of Huh7 cells in order to provide new ideas for the clinical combined therapy of hepatocellular carcinoma. Methods: The Huh7 cells silencing GRAMD1A was constructed by infecting lentivirus and verified by qPCR and Western blot. QPCR and luciferase reporter assays were used to detect the effect of silencing GRAMD1A on the expression of STAT5 and its downstream genes. Colony formation and apoptosis were detected to evaluate the effects of silencing GRAMD1A and STAT5 inhibitor SH-4-54 on cell radiosensitivity. Results: After 2 Gy exposure of the constructed Huh7 cells, the colony formation ability of the silencing GRAMD1A combined irradiation group was significantly lower than that of the negative control combined irradiation group, and the difference was statistically significant (t=8. 494, P<0.05). Silence apoptosis in the GRAMD1A combined irradiation group was significantly increased compared with the negative control combined irradiation group (t=3.560, P<0.05). After silencing GRAMD1A, the radiosensitivity of Huh7 cells was significantly increased, and the expression of STAT5 and its downstream genes was significantly reduced in cells.The survival rate of the SH-4-54 inhibitor combined irradiation group was significantly lower than that of the dimethyl sulfoxide combined irradiation group, and the difference was statistically significant (t=8.660, P<0.05). SH-4-54 inhibited STAT5 after passage, the radiosensitivity of Huh7 cells was significantly increased. Conclusions Silencing GRAMD1A could significantly enhance the radiosensitivity of Huh7 cells via STAT5 signaling pathway, indicating that GRAMD1A plays an important role in the development and progression of HCC. This finding may provide a new target for HCC therapy.