摘要:Background and purpose: It has been reported that mammalian Ste20-like kinase 4 (MST4) promotes the invasion and metastasis of tumors. In the previous research, we found that MST4 promoted invasion and metastasis of liver cancer through epithelial-mesenchymal transition. In this study, we explored the effect of MST4 on promoting the invasion and metastasis of hepatocellular carcinoma (HCC) cells by activating MAPK-ERK signaling pathway and inflammatory factors. Methods: We used real-time fluorescence quantitative polymerase chain reaction (RTFQ-PCR) to detect the transcription of IL-1β, IL-6, TNF-α and CCL2 in different HCC cell lines expressing MST4 differently. Then we studied the different secretion of IL-1β, IL-6, TNF-α and CCL2 in cells using Western blot and enzyme-linked immunosorbent assay (ELISA). Results: The RNA transcription and protein translation levels of IL-1β, IL-6, TNF-α and CCL2 were significantly higher in HCC cell line with high expression of MST4 than those in the HCC cell line with lower expression of MST4 (P<0.05). We found that MST4 could change the level of phosphorylation of ERK to promote secretion of inflammatory cytokines. Conclusion: High expression of MST4 can upregulate the secretion of inflammatory factors (IL-1β, IL-6, TNF-α and CCL2) in HCC cells and enhance the ability of invasion and metastasis of HCC cells, through activating the MAPK-ERK signaling pathway.
关键词:Mammalian Ste20-like kinase 4;Hepatocellular carcinoma;Inflammatory factors;Invasion and metastasis
摘要:Background and purpose: Patient with metastatic soft tissue sarcoma has a poor prognosis with median survival time of less than 1 year. Doxorubicin combined with ifosfamide (IFO) (AI regimen) is frequently used in the first-line treatment for patients with metastatic soft tissue sarcoma. Pegylated liposomal doxorubicin (PLD) is the liposomal formulation of doxorubicin and has exhibited less toxicity. Therefore our study was aimed to evaluate the efficacy and safety of PLD combined with IFO as the first-line treatment for patients with advanced or metastatic soft tissue sarcoma (STS). Methods: A total of 25 chemotherapy-naive patients with advanced or metastatic STS were enrolled in this study between November 2013 and December 2015. All patients received treatment of PLD 30 mg/m2, d1, plus IFO 1.8 g/m2, d1-5, repeatedly every 21 days. Results: All patients received 1-8 cycles of treatment, at a median of 4 cycles. Among 25 patients, partial response was observed in 9 patients (36%), stable disease (SD) was observed in 12 patients (48%) and progressive disease (PD) in 4 patients (16%). The disease control rate (DCR, CR+PR+SD) was 84%. The median progression-free survival (PFS) was 7.3 months (95%CI, 4.6 to 10.0 months). The grade 3/4 toxicities included leukopenia (20%), neutropenia (28%), anemia (4%) and vomiting (4%). Conclusion: Combination therapy comprising PLD and IFO was effective and well tolerated as first-line treatment for patients with advanced or metastatic STS, which warrants further research.