Apatinib exerts anti-tumor activity to non-Hodgkin lymphoma by inhibition of the Ras pathway

Wang, Yan; Deng, Manman; Chen, Qinwei; Li, Yin; Guo, Xutao; Shi, Pengcheng; He, Lingli; Xie, Siting; Yu, Lian; Zhang, Haiping

doi:10.1016/j.ejphar.2018.11.012

Cited by 12 publications

(12 citation statements)

References 32 publications

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“…Apatinib, a highly selective tyrosine kinase inhibitor to VEGFR2, has been reported to exert antitumor effects in various types of tumors, such as osteosarcoma, thyroid cancer, cervical cancer and gastric cancer (7,8,23,24). The present study aimed to demonstrate the potential antitumor effects of apatinib in NB cells in vitro.…”

Section: Discussionmentioning

confidence: 94%

Apatinib induces apoptosis and autophagy via the PI3K/AKT/mTOR and MAPK/ERK signaling pathways in neuroblastoma

Fan

Jiang

et al. 2020

Oncol Lett

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The clinical outcome of neuroblastoma (NB) has significantly improved in the last 30 years for patients with localized disease; however, the overall survival (OS) for patients with metastasis remains poor. Apatinib, a selective inhibitor of the vascular endothelial growth factor receptor-2 (VEGFR-2) tyrosine kinase, which was discovered to be highly associated with metastasis, has been reported to exert antitumor effects in numerous types of cancer. However, the effect of apatinib in NB remains relatively unknown. The present study aimed to investigate the antitumor effects of apatinib in NB cells in vitro. The results revealed that apatinib inhibited cell viability and colony formation, whilst inducing cell cycle arrest and the apoptosis of NB cells. Additionally, apatinib inhibited the migration and invasion of NB cells, in addition to promoting the autophagy of NB cells. Western blotting demonstrated that the protein expression levels of phosphorylated (p)-AKT, p-mTOR and p-P70S6K, and downstream molecules associated with the cell cycle and apoptosis, such as cyclin D1 and the Bcl-2/Bax ratio of NB cells, were significantly decreased following treatment with apatinib. In addition, western blotting and immunofluorescence assays identified that the expression level of microtubule-associated protein 1A/1B-light chain 3-II, which is expressed in autophagosomes, was upregulated following apatinib treatment. In conclusion, the findings of the present study suggested that apatinib may induce apoptosis and autophagy via the PI3K/AKT/mTOR and mitogen-activated protein kinase/ERK signaling pathways in NB cells. Thus, apatinib may be a potential antitumor agent for the clinical treatment of NB.

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Section: Discussionmentioning

confidence: 94%

Apatinib induces apoptosis and autophagy via the PI3K/AKT/mTOR and MAPK/ERK signaling pathways in neuroblastoma

Fan

Jiang

et al. 2020

Oncol Lett

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“…This result accords with the findings of a preclinical study that apatinib exhibited similar anti-tumour activity in both DLBCL subtypes. 13 These results provided valuable experience for other investigators to determine their preferable initial dose and treatment cycle.…”

Section: Discussionmentioning

confidence: 89%

“…17 Apatinib has therapeutic potential for DLBCL by blocking the intracellular adenosine triphosphate-binding site of VEGFR-2, inhibiting VEGFR-2 autophosphorylation and downstream Ras/Raf/MEK/ERK and PI3K pathway activation, thereby interfering with tumourigenesis and progression. 13,18 Wang et al reported the anti-tumour activity of apatinib in DLBCL (both GCB and ABC subtypes) in a preclinical setting. 13 Apatinib showed cytotoxicity and induced apoptosis in DLBCL cell lines (OCI-ly1, OCI-ly3, SU-DHL-2, and SU-DHL-4), and significantly suppressed tumour progression and prolonged survival in a xenograft mouse model without obvious bodyweight loss, indicating the efficacy and tolerability of apatinib.…”

Section: Discussionmentioning

confidence: 99%

“…13,18 Wang et al reported the anti-tumour activity of apatinib in DLBCL (both GCB and ABC subtypes) in a preclinical setting. 13 Apatinib showed cytotoxicity and induced apoptosis in DLBCL cell lines (OCI-ly1, OCI-ly3, SU-DHL-2, and SU-DHL-4), and significantly suppressed tumour progression and prolonged survival in a xenograft mouse model without obvious bodyweight loss, indicating the efficacy and tolerability of apatinib. This study also showed that apatinib down-regulated several Ras pathway targets and had a kinase inhibitory effect on c-Src, c-Kit, and PDGFRb besides VEGFR-2, which may also contribute to cytotoxicity in vitro and anti-angiogenesis in vivo of apatinib in DLBCL.…”

Section: Discussionmentioning

confidence: 99%

“…Laboratory work shows that apatinib inhibits the proliferation of various NHL cell lines in a dose-dependent manner and significantly postpone tumour growth and prolong the survival of xenograft mice model derived from human DLBCL cells. 13 Additionally, we had conducted a clinical trial on apatinib for relapse or refractory NHL (RR NHL) in our centre. We enrolled 27 patients with RR NHL, including 11 patients with RR DLBCL, accounting for an ORR of 47.6%, suggesting an anti-tumour effect of apatinib to improve the response rate and survival of patients with RR NHL.…”

Section: Introductionmentioning

confidence: 99%

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<p>Apatinib in Patients with Relapsed or Refractory Diffuse Large B Cell Lymphoma: A Phase II, Open-Label, Single-Arm, Prospective Study</p>

Zhang

et al. 2020

DDDT

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These authors contributed equally to this work Purpose: Treatment options for relapsed or refractory diffuse large B-cell lymphoma (RR DLBCL) represent an unmet medical need. Apatinib is a new oral tyrosine kinase inhibitor mainly targeting vascular endothelial growth factor receptor-2 (VEGFR-2) to inhibit tumour angiogenesis. In the present study, we evaluated the efficacy and safety of apatinib for patients with RR DLBCL. Patients and Methods: In this phase II, open-label, single-arm, prospective study, we enrolled patients aged 14-70 years with treatment failure of at least two chemotherapeutic regimens using Simon's two-stage design. All patients were administered apatinib at an initial dose of 500 mg on a 4-week cycle at home and visited the outpatient clinic every two cycles to evaluate efficacy and to record adverse events. We considered objective response rate (ORR) as the primary end point, and progression-free survival (PFS), and overall survival (OS) plus duration of response (DoR) as the secondary end point. (This trial was registered at ClinicalTrials.gov, identifier: NCT03376958.). Results: From January 2017 to February 2019, we screened 35 patients and enrolled 32 eligible patients. At the cutoff point (April 2019), we noted 2 (6.3%) complete responses, 12 (37.5%) partial responses, and 9 (28.1%) stable diseases, attributing to an ORR of 43.8% and a disease control rate of 71.9%. The median PFS and OS were 6.9 (95% confidence interval [CI], 5.8-7.9) and 7.9 months (95% CI, 7.0-8.7), respectively. The median DoR was 5.0 months (95% CI, 3.5-6.5) for patients who achieved PR. The most common grade 3-4 adverse events (AE) were hypertension (12.6%), hand-foot syndrome (9.4%), and leucopenia (6.3%). No apatinib-related deaths were noted. Conclusion: Home administration of apatinib shows promising efficacy and manageable AEs in patients with RR DLBCL.

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Targeting tumor vascularization: promising strategies for vascular normalization

Zheng

Gong

2021

J Cancer Res Clin Oncol

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Apatinib exerts anti-tumor activity to non-Hodgkin lymphoma by inhibition of the Ras pathway

Cited by 12 publications

References 32 publications

Apatinib induces apoptosis and autophagy via the PI3K/AKT/mTOR and MAPK/ERK signaling pathways in neuroblastoma

Apatinib induces apoptosis and autophagy via the PI3K/AKT/mTOR and MAPK/ERK signaling pathways in neuroblastoma

<p>Apatinib in Patients with Relapsed or Refractory Diffuse Large B Cell Lymphoma: A Phase II, Open-Label, Single-Arm, Prospective Study</p>

Targeting tumor vascularization: promising strategies for vascular normalization

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