Inhibition of proliferation and induction of apoptosis in RB116 retinoblastoma cells by afatinib treatment

Zhan, Wei-Jiao; Zhu, Jianfeng; Wang, Long-mei

doi:10.1007/s13277-015-4768-1

Cited by 7 publications

(5 citation statements)

References 18 publications

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“…Previous studies reported that afatinib can inhibit cell proliferation and induce apoptosis in various types of cancer cells [29–31]. To explore whether afatinib could induce apoptosis in NB cells, IMR-32, NGP, NB-19, SK-N-AS, SH-SY5Y, and LA-N-6 cells were treated with afatinib for various time points (0-16 hrs).…”

Section: Resultsmentioning

confidence: 99%

Novel multi-targeted ErbB family inhibitor afatinib blocks EGF-induced signaling and induces apoptosis in neuroblastoma

et al. 2016

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Neuroblastoma is the most common extracranial solid tumor in children. The ErbB family of proteins is a group of receptor tyrosine kinases that promote the progression of various malignant cancers including neuroblastoma. Thus, targeting them with small molecule inhibitors is a promising strategy for neuroblastoma therapy. In this study, we investigated the anti-tumor effect of afatinib, an irreversible inhibitor of members of the ErbB family, on neuroblastoma. We found that afatinib suppressed the proliferation and colony formation ability of neuroblastoma cell lines in a dose-dependent manner. Afatinib also induced apoptosis and blocked EGF-induced activation of PI3K/AKT/mTOR signaling in all neuroblastoma cell lines tested. In addition, afatinib enhanced doxorubicin-induced cytotoxicity in neuroblastoma cells, including the chemoresistant LA-N-6 cell line. Finally, afatinib exhibited antitumor efficacy in vivo by inducing apoptosis in an orthotopic xenograft neuroblastoma mouse model. Taken together, these results show that afatinib inhibits neuroblastoma growth both in vitro and in vivo by suppressing EGFR-mediated PI3K/AKT/mTOR signaling. Our study supports the idea that EGFR is a potential therapeutic target in neuroblastoma. And targeting ErbB family protein kinases with small molecule inhibitors like afatinib alone or in combination with doxorubicin is a viable option for treating neuroblastoma.

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Section: Resultsmentioning

confidence: 99%

Novel multi-targeted ErbB family inhibitor afatinib blocks EGF-induced signaling and induces apoptosis in neuroblastoma

et al. 2016

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“…We first observed growth inhibition and apoptosis in afatinib-treated H1975 and H1650 cells. Many studies prove that the TKI-induced apoptosis is caspase 3 dependent 38 , 39 , and it has been reported that afatinib could induce H1975, H1650 and RB116 cell apoptosis by activation of caspase 3 40 , 41 . Our experiments proved that afatinib dramatically increased casepase 3 activity, and pan-caspase inhibitor z-VAD-fmk could rescue the cells and decrease caspase 3 activity as well as the level of cleaved-PARP.…”

Section: Discussionmentioning

confidence: 99%

Blocking autophagy improves the anti-tumor activity of afatinib in lung adenocarcinoma with activating EGFR mutations in vitro and in vivo

Shi

Wang

et al. 2017

Sci Rep

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Afatinib, a second-generation tyrosine kinase inhibitor (TKI), has been approved for the treatment of advanced EGFR-mutant non-small cell lung cancer (NSCLC). However, afatinib’s clinical application is still hampered by acquired resistance. Recently, autophagy is considered as an important mechanism of resistance to TKI. Herein, we investigated the autophagy induction as well as its influence on anti-lung adenocarcinoma activity of afatinib in two activating EGFR-mutants H1975 and H1650 cells. First, Growth inhibition and caspase-dependent apoptosis were observed in afatinib-treated H1975 and H1650 cells. Then we confirmed afatinib-induced autophagy in H1975 and H1650 cells. Importantly, autophagy inhibition using chloroquine (CQ) and 3-MA enhanced the cytotoxicity of afatinib, elucidating the cytoprotective role of autophagy in lung adenocarcinoma therapy with afatinib. Further study suggested that Akt/mTOR and Erk signaling pathways were involved in afatinib-induced autophagy, and reactive oxygen species (ROS) acted as an intracellular transducer regulating both autophagy and apoptosis in afatinib-treated H1975 and H1650 cells. Moreover, the in vivo experiment in xenograft model using H1975 cell line confirmed the enhanced anti-lung adenocarcinoma efficacy of afatinib when combined with autophagy inhibitor CQ. Thus, blocking autophagy may be a promising strategy to overcome resistance and increase sensitivity to afatinib in lung adenocarcinoma harboring activating EGFR mutations.

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“…Up to date, there are a few studies on the use of tyrosine kinase inhibitors against retinoblastoma. Available data demonstrated good outcomes achieved in vitro with the use of afatinib, erlotinib (both are EGFR inhibitors), and imatinib (PDGFRA and PDGFRB inhibitor) [53][54][55].…”

Section: Tyrosine Kinase Inhibitorsmentioning

confidence: 99%

The Role of Intraarterial Chemotherapy in the Management of Retinoblastoma

Pekacka

2020

Journal of Ophthalmology

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Introduction. Retinoblastoma is the most common primary intraocular neoplasm in children. With the advances in medicine, the armamentarium of available treatment modalities has grown. Intraarterial chemotherapy is a relatively new treatment method with promising outcomes. The purpose of this literature review is to evaluate its role in the management of retinoblastoma. Methods. A systematic online search was conducted using Ovid Embase and Ovid Medline. The final results included 23 studies. The studies were published between 2011 and 2019. The studies evaluated the technical success rate of IAC, globe salvage rate, and ocular and systemic complications, as well as the occurrence of deaths, metastasis, and secondary neoplasms. In total, 1827 eyes with retinoblastoma were analysed. The follow-up was between 0 and 252 months. Results. Overall globe retention rate ranged from 30% to 100%. Sixteen out of 23 studies reported ocular salvage between 60 and 80%. Eyelid oedema and erythema were the most commonly reported ocular complications following IAC. The most common systemic complications included nausea, vomiting, and neutropenia. Metastases and deaths were reported in 6 out of 23 studies. Three studies reported the development of secondary neoplasms. The technical success rate of IAC procedure ranged from 91% to 100%. Discussion. The studies have shown that IAC is a safe and effective treatment for advanced retinoblastoma, especially group D. It allows to save the globe without compromising patients’ survival. Local and systemic complications are acceptable. The role of IAC in less advanced tumours is yet to be established. Future work should focus on conducting larger prospective studies with longer follow-up. Multiple novel therapies for the management of retinoblastoma are currently being tested, including angiogenic inhibitors and targeted agents. The results seem to be promising. Future advances require a further in-depth understanding of unique genetics of retinoblastoma and complex interactions between tumour cells and their microenvironment.

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Inhibition of proliferation and induction of apoptosis in RB116 retinoblastoma cells by afatinib treatment

Cited by 7 publications

References 18 publications

Novel multi-targeted ErbB family inhibitor afatinib blocks EGF-induced signaling and induces apoptosis in neuroblastoma

Novel multi-targeted ErbB family inhibitor afatinib blocks EGF-induced signaling and induces apoptosis in neuroblastoma

Blocking autophagy improves the anti-tumor activity of afatinib in lung adenocarcinoma with activating EGFR mutations in vitro and in vivo

The Role of Intraarterial Chemotherapy in the Management of Retinoblastoma

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