Inhibition of SRC/FAK cue: A novel pathway for the synergistic effect of rosuvastatin on the anti-cancer effect of dasatinib in hepatocellular carcinoma

Sayed, Ibrahim El Tantawy El; Helmy, Maged W.; El‐Abhar, Hanan S.

doi:10.1016/j.lfs.2018.10.002

Cited by 35 publications

(22 citation statements)

References 56 publications

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“…Moreover, in mouse and human HCC cell lines, treatment with fluvastatin, simvastatin, atorvastatin, rosuvastatin or lovastatin are all associated with induced cellular apoptosis in a p53 dependent manner [35]. Modulation other molecular pathways, such as inhibition of signal transducer and activator of transcription 3/SKP2 axis [36], inhibition of SRC/FAK cue [37], and activation of AMPK et al [38] have also been involved in the potential anti-HCC effects of statins. The key mechanisms underlying the potential anti-HCC efficacy of statins in patients with HBV or HCV infection deserve further investigations.…”

Section: Discussionmentioning

confidence: 99%

Statin and the risk of hepatocellular carcinoma in patients with hepatitis B virus or hepatitis C virus infection: a meta-analysis

Li¹,

Sheng²,

Liu³

et al. 2020

BMC Gastroenterol

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Background: Statin may confer anticancer effect. However, the association between statin and risk of hepatocellular carcinoma (HCC) in patients with hepatitis B virus (HBV) or hepatitis C (HCV) virus infection remains inconsistent according to results of previous studies. A meta-analysis was performed to summarize current evidence. Methods: Related follow-up studies were obtained by systematic search of PubMed, Cochrane's Library, and Embase databases. A random-effect model was used to for the meta-analysis. Stratified analyses were performed to evaluate the influences of study characteristics on the outcome. Results: Thirteen studies with 519,707 patients were included. Statin use was associated with reduced risk of HCC in these patients (risk ratio [RR]: 0.54, 95% CI: 0.44 to 0.66, p < 0.001; I 2 = 86%). Stratified analyses showed that the association between statin use and reduced HCC risk was consistent in patients with HBV or HCV infection, in elder (≥ 50 years) or younger (< 50 years) patients, in males or females, in diabetic or non-diabetic, and in those with or without cirrhosis (all p < 0.05). Moreover, lipophilic statins was associated with a reduced HCC risk (RR: 0.52, p < 0.001), but not for hydrophilic statins (RR: 0.89, p = 0.21). The association was more remarkable in patients with highest statin accumulative dose compared to those with lowest accumulative dose (p = 0.002). Conclusions: Satin use was independently associated with a reduced risk of HCC in patients with HBV or HCV infection.

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Section: Discussionmentioning

confidence: 99%

Statin and the risk of hepatocellular carcinoma in patients with hepatitis B virus or hepatitis C virus infection: a meta-analysis

Li¹,

Sheng²,

Liu³

et al. 2020

BMC Gastroenterol

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show abstract

“…Besides, treatment with fluvastatin, simvastatin, atorvastatin, rosuvastatin, or lovastatin were all associated with induced cellular apoptosis in mouse and human HCC cell lines in a p53 dependent manner [30]. In addition, other molecular pathways, such as inhibition of signal transducer and activator of transcription 3/SKP2 axis [31], inhibition of SRC/FAK cue [32], and activation of AMPK et al [33] have also been involved in the potential anti-HCC effects of statins. Besides, many other benefits of statins in patients with hepatic disorders, such as cirrhosis, have also been noticed.…”

Section: Discussionmentioning

confidence: 99%

Statin use and the prognosis of patients with hepatocellular carcinoma: a meta-analysis

Li¹,

Liu²,

Hu³

2020

Bioscience Reports

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Background: Association between statin use and prognosis in patients with hepatocellular carcinoma (HCC) remains unknown. We performed a meta-analysis of follow-up studies to systematically evaluate the influence of statin use on clinical outcome in HCC patients. Methods: Studies were obtained via systematic search of PubMed, Cochrane’s Library, and Embase databases. A randomized-effect model was used to pool the results. Subgroup analyses were performed to evaluate the influence of study characteristics on the association. Results: Nine retrospective cohort studies were included. Overall, statin use was associated with a reduced all-cause mortality in HCC patients (risk ratio [RR]: 0.81, 95% CI: 0.74–0.88, P < 0.001; I2 = 63%). Subgroup analyses showed similar results for patients with stage I-III HCC (RR: 0.83, 0.79, and 0.90 respectively, P all < 0.01) and patients after palliative therapy for HCC (RR: 0.80, P < 0.001), but not for patents with stage IV HCC (RR: 0.91, P = 0.28) or those after curative therapy (RR: 0.92, P = 0.20). However, the different between subgroups were not significant (both P > 0.05). Moreover, statin use was associated with reduced HCC-related mortality (RR: 0.78, P = 0.001) in overall patient population and HCC recurrence in patients after curative therapies (RR: 0.55, P < 0.001). Conclusions: Satin use is associated with reduced mortality and recurrence of HCC. These results should be validated in prospective cohort studies and randomized controlled trials.

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“…Recent evidence suggested that FAK could provide a binding site for Src and other molecules when FAK was activated via phosphorylation [25]. Subsequently, the phosphorylated FAK could promote expression of the downstream signalling mediators, including Raf and Ras, which plays a significant role in the regulation of cell adhesion, migration, cell spreading and differentiation [26].…”

Section: Discussionmentioning

confidence: 99%

FAK mediates BMP9-induced osteogenic differentiation via Wnt and MAPK signaling pathway in synovial mesenchymal stem cells

Zheng

Sun

et al. 2019

Artificial Cells, Nanomedicine, and Biotechnology

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Objective: Focal adhesion kinase (FAK) has critical functions in proliferation and differentiation of many cell types, however, the role of FAK on BMP9-induced osteogenic differentiation in SMSCs has not been characted. The purpose of current study is to explore the mechanism of FAK on the BMP9induced osteogenesis of SMSCs in vitro and in vivo. Methods: The optimal dose of BMP9 was determined by incubation in different BMP9 concentrations, then cells were transfected with siRNA-induced FAK knockdown in BMP9-induced osteogenesis. Cell proliferation, migration, the osteogenic capacity, and the underlying mechanism were further detected in vitro. Imaging and pathological examination were conducted to observe the bone formation in vivo. Results: Our findings suggested that BMP9 could obviously promote FAK phosphorylation in osteogenic conditions. In contrast, FAK knockdown significantly decreased the cell proliferation, migration, the osteogenic capacity of SMSCs. To be specific, FAK knockdown could markedly inhibit the Wnt and MAPK signal pathway of SMSCs induced by BMP9. Besides, FAK knockdown could also effectively inhibit BMP-9-induced bone formation in vivo. Conclusion: FAK plays a pivotal role in promoting BMP9-induced osteogenesis of SMSCs, which is probably via activating Wnt and MAPK pathway.

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Inhibition of SRC/FAK cue: A novel pathway for the synergistic effect of rosuvastatin on the anti-cancer effect of dasatinib in hepatocellular carcinoma

Cited by 35 publications

References 56 publications

Statin and the risk of hepatocellular carcinoma in patients with hepatitis B virus or hepatitis C virus infection: a meta-analysis

Statin and the risk of hepatocellular carcinoma in patients with hepatitis B virus or hepatitis C virus infection: a meta-analysis

Statin use and the prognosis of patients with hepatocellular carcinoma: a meta-analysis

FAK mediates BMP9-induced osteogenic differentiation via Wnt and MAPK signaling pathway in synovial mesenchymal stem cells

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