Multiple CDK inhibitor dinaciclib suppresses neuroblastoma growth via inhibiting CDK2 and CDK9 activity

Chen, Zhenghu; Wang, Zhenyu; Pang, Ji‐Jie; Ye, Yu; Bieerkehazhi, Shayahati; Lu, Jian; Hu, Tian; Zhao, Yanling; Xu, Xin; Zhang, Hong; Yi, Joanna; Liu, Shangfeng; Yang, Jianhua

doi:10.1038/srep29090

Cited by 62 publications

(54 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Female athymic NCR nude mice were purchased from Taconic (Taconic, Hudson, NY, USA) and maintained under pathogen-free conditions. The preclinical mouse model of NB was established using orthotopic (intrarenal) implantation of the NB cells as described previously [9]. 1.5 × 10 6 human luciferase -transduced NGP cells in 0.1 ml of PBS were surgically injected into the left renal capsule and toward the superior pole of the left kidney of the animal.…”

Section: Methodsmentioning

confidence: 99%

The second-generation ALK inhibitor alectinib effectively induces apoptosis in human neuroblastoma cells and inhibits tumor growth in a TH-MYCN transgenic neuroblastoma mouse model

Guan

Zhao

et al. 2017

Cancer Letters

Self Cite

View full text Add to dashboard Cite

Activating germline mutations of anaplastic lymphoma kinase (ALK) occur in most cases of hereditary neuroblastoma (NB) and the constitutively active kinase activity of ALK promotes cell proliferation and survival in NB. Therefore, ALK kinase is a potential therapeutic target for NB. In this study, we show that the novel ALK inhibitor alectinib effectively suppressed cell proliferation and induces apoptosis in NB cell lines with either wild-type ALK or mutated ALK (F1174L and D1091N) by blocking ALK-mediated PI3K/Akt/mTOR signaling. In addition, alectinib enhanced doxorubicin-induced cytotoxicity and apoptosis in NB cells. Furthermore, alectinib induced apoptosis in an orthotopic xenograft NB mouse model. Also, in the TH-MYCN transgenic mouse model, alectinib resulted in decreased tumor growth and prolonged survival time. These results indicate that alectinib may be a promising therapeutic agent for the treatment of NB.

show abstract

Section: Methodsmentioning

confidence: 99%

The second-generation ALK inhibitor alectinib effectively induces apoptosis in human neuroblastoma cells and inhibits tumor growth in a TH-MYCN transgenic neuroblastoma mouse model

Guan

Zhao

et al. 2017

Cancer Letters

Self Cite

View full text Add to dashboard Cite

show abstract

“…The preclinical mouse model of NB was established using orthotopic (intrarenal) implantation of the NB cells as described previously505152. Briefly, a transverse incision was created over the left flank of the nude mouse and 1.5 × 10 6 human luciferase-transduced SH-SY5Y cells in 0.1 ml of PBS were surgically injected into the left renal capsule and toward the superior pole of the left kidney of the nude mice.…”

Section: Methodsmentioning

confidence: 99%

Wip1 inhibitor GSK2830371 inhibits neuroblastoma growth by inducing Chk2/p53-mediated apoptosis

Chen

Wang

Yao

et al. 2016

Sci Rep

Self Cite

View full text Add to dashboard Cite

Neuroblastoma (NB) is the most common extracranial tumor in children. Unlike in most adult tumors, tumor suppressor protein 53 (p53) mutations occur with a relatively low frequency in NB and the downstream function of p53 is intact in NB cell lines. Wip1 is a negative regulator of p53 and hindrance of Wip1 activity by novel inhibitor GSK2830371 is a potential strategy to activate p53’s tumor suppressing function in NB. Yet, the in vivo efficacy and the possible mechanisms of GSK2830371 in NB have not yet been elucidated. Here we report that novel Wip1 inhibitor GSK2830371 induced Chk2/p53-mediated apoptosis in NB cells in a p53-dependent manner. In addition, GSK2830371 suppressed the colony-formation potential of p53 wild-type NB cell lines. Furthermore, GSK2830371 enhanced doxorubicin- (Dox) and etoposide- (VP-16) induced cytotoxicity in a subset of NB cell lines, including the chemoresistant LA-N-6 cell line. More importantly, GSK2830371 significantly inhibited tumor growth in an orthotopic xenograft NB mouse model by inducing Chk2/p53-mediated apoptosis in vivo. Taken together, this study suggests that GSK2830371 induces Chk2/p53-mediated apoptosis both in vitro and in vivo in a p53 dependent manner.

show abstract

“…The preclinical xenograft mouse model of NB was established using an orthotopic (intrarenal) implantation of the NB cells as described previously [62–64]. Briefly, 1.5 × 10 6 human luciferase-transduced SH-SY5Y cells was kept in 0.1 mL of PBS and a transverse incision was generated over the left flank of the nude mouse.…”

Section: Methodsmentioning

confidence: 99%

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

et al. 2016

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Multiple CDK inhibitor dinaciclib suppresses neuroblastoma growth via inhibiting CDK2 and CDK9 activity

Cited by 62 publications

References 57 publications

The second-generation ALK inhibitor alectinib effectively induces apoptosis in human neuroblastoma cells and inhibits tumor growth in a TH-MYCN transgenic neuroblastoma mouse model

The second-generation ALK inhibitor alectinib effectively induces apoptosis in human neuroblastoma cells and inhibits tumor growth in a TH-MYCN transgenic neuroblastoma mouse model

Wip1 inhibitor GSK2830371 inhibits neuroblastoma growth by inducing Chk2/p53-mediated apoptosis

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

Contact Info

Product

Resources

About