Lenvatinib induces death of human hepatocellular carcinoma cells harboring an activated FGF signaling pathway through inhibition of FGFR–MAPK cascades

Hoshi, Taisuke; Miyano, Saori Watanabe; Watanabe, Hideki; Sonobe, Regina Mikie Kanada; Seki, Yasutaka; Ohta, Etsuko; Nomoto, Ken’ichi; Matsui, Junji; Funahashi, Yasuhiro

doi:10.1016/j.bbrc.2019.02.015

Cited by 61 publications

(39 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Nonetheless, it should be noted that lenvatinib has no effect on either the proliferation and survival of T cells or the proliferation, cell cycle, and apoptosis of tumor cells. Previous studies suggested that lenvatinib could inhibit the growth of tumor cells by targeting the autocrine FGF-FGFR pathway [24,31]. Our results, however, show that lenvatinib has no significant effect on tumor cell growth at a relatively low concentration, but it rather acts as an immunoregulator.…”

Section: Discussioncontrasting

confidence: 78%

Dual Vascular Endothelial Growth Factor Receptor and Fibroblast Growth Factor Receptor Inhibition Elicits Antitumor Immunity and Enhances Programmed Cell Death-1 Checkpoint Blockade in Hepatocellular Carcinoma

et al. 2020

View full text Add to dashboard Cite

show abstract

Section: Discussioncontrasting

confidence: 78%

Dual Vascular Endothelial Growth Factor Receptor and Fibroblast Growth Factor Receptor Inhibition Elicits Antitumor Immunity and Enhances Programmed Cell Death-1 Checkpoint Blockade in Hepatocellular Carcinoma

et al. 2020

View full text Add to dashboard Cite

show abstract

“…31 Lenvatinib inhibited angiogenesis and induced cell death in HCC by suppressing FGFR signaling pathways or FGFR-MAPK cascades. 32,33 Consistent with these findings, we discovered that FGFR1 was highly expressed in HCC tissues and cells. Besides, FGFR1 overexpression abolished the effects of miR-610 enrichment, leading to HCC malignant development.…”

Section: Discussionsupporting

confidence: 83%

<p>Circ_0015756 Aggravates Hepatocellular Carcinoma Development by Regulating FGFR1 via Sponging miR-610</p>

Guo

Zhao

Wei

et al. 2020

CMAR

View full text Add to dashboard Cite

Background: Hepatocellular carcinoma (HCC) is the leading threat of cancer-related death in humans. Increasing studies show that circular RNAs (circRNAs) are important indicators in cancer diagnosis and prognosis. This study intended to explore the function and mechanism of circ_0015756 in HCC, providing the additional opinion for HCC treatment. Materials and Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was utilized to detect the expression of circ_0015756 and miR-610. Cell viability was assessed by cell counting kit-8 (CCK-8) assay, and colony formation capacity was ascertained by colony formation assay. Cell migration and invasion were monitored by transwell assay. Cell cycle progression and apoptosis were analyzed by flow cytometry assay. Circ_0015756 oncogenicity was determined by Xenograft models. The targets of circ_0015756 and miR-610 were predicted by bioinformatics tools and validated using RNA pull-down, RNA immunoprecipitation (RIP) and dual-luciferase reporter assays. The expression level of fibroblast growth factor receptor 1 (FGFR1) was measured by Western blot. Results: The expression of circ_0015756 was increased in HCC tissues, serums and cells. Circ_0015756 downregulation impaired HCC cell viability, colony formation capacity, invasion and migration, induced cell cycle arrest and apoptosis, and inhibited tumor growth in vivo. MiR-610 was ensured as a target of circ_0015756, and miR-610 absence reversed the effects of circ_0015756 downregulation. Further, FGFR1 was targeted by miR-610, and FGFR1 overexpression overturned the effects of miR-610 restoration in HCC cells. Circ_0015756 could regulate FGFR1 expression by targeting miR-610. Conclusion: Circ_0015756 played its tumorigenic properties in HCC by activating FGFR1 via sponging miR-610, and circ_0015756 was expected to be a vital indicator in HCC diagnosis and treatment.

show abstract

“…Serum VEGF and FGF levels are reportedly increased following treatment with TACE and seem to affect patient survival ( 33 ). Lenvatinib is a potent inhibitor of VEGFR1-3 and pro-oncogenic receptor tyrosine kinases, including FGFR1-4 ( 12 , 34 , 35 ). In addition, the IC 50 of lenvatinib for VEGFR and FGFR is lower than that of sorafenib ( 36 ).…”

Section: Discussionmentioning

confidence: 99%

Lenvatinib prolongs the progression‑free survival time of patients with intermediate‑stage hepatocellular carcinoma refractory to transarterial chemoembolization: A multicenter cohort study using data mining analysis

et al. 2020

View full text Add to dashboard Cite

Tyrosine kinase inhibitors are considered for use in patients with hepatocellular carcinoma (HCC) refractory to transarterial chemoembolization (TACE). The aim of the present retrospective study was to identify factors associated with progression-free survival (PFS) and to evaluate the indications for lenvatinib treatment in patients with intermediate-stage HCC refractory to TACE using a data-mining analysis. A total of 171 patients with intermediate-stage HCC refractory to TACE were included. All patients were classified into three groups according to their HCC treatment: Lenvatinib (n=45), sorafenib (n=53) and TACE (n=73) groups. PFS time was calculated using the Kaplan-Meier method and analyzed using a log-rank test. Factors associated with PFS time were evaluated using multivariate and decision-tree analyses. The median PFS time was 5.8, 3.2 and 2.4 months in the lenvatinib, sorafenib and TACE groups, respectively (P<0.001). In the Cox regression analysis, lenvatinib treatment and being within the up-to-seven criteria were identified as independent factors for PFS (lenvatinib, P<0.0001; within up-to-seven, P=0.001). The decision-tree analysis revealed that patients beyond the up-to-seven criteria, treated with lenvatinib and with albumin-bilirubin (ALBI) grade 1 had a longer PFS time (245.2±107.9 days) than patients beyond the up-to-seven criteria, treated with lenvatinib and with ALBI grade 2 (147.1±78.6 days). Additionally, lenvatinib was independently associated with longer PFS time in patients with intermediate-stage HCC refractory to TACE. Therefore, lenvatinib may be recommended for patients who have intermediate-stage HCC refractory to TACE, ALBI grade 1 and who are within the up-to-seven criteria.

show abstract

Lenvatinib induces death of human hepatocellular carcinoma cells harboring an activated FGF signaling pathway through inhibition of FGFR–MAPK cascades

Cited by 61 publications

References 23 publications

Dual Vascular Endothelial Growth Factor Receptor and Fibroblast Growth Factor Receptor Inhibition Elicits Antitumor Immunity and Enhances Programmed Cell Death-1 Checkpoint Blockade in Hepatocellular Carcinoma

Dual Vascular Endothelial Growth Factor Receptor and Fibroblast Growth Factor Receptor Inhibition Elicits Antitumor Immunity and Enhances Programmed Cell Death-1 Checkpoint Blockade in Hepatocellular Carcinoma

<p>Circ_0015756 Aggravates Hepatocellular Carcinoma Development by Regulating FGFR1 via Sponging miR-610</p>

Lenvatinib prolongs the progression‑free survival time of patients with intermediate‑stage hepatocellular carcinoma refractory to transarterial chemoembolization: A multicenter cohort study using data mining analysis

Contact Info

Product

Resources

About