Anlotinib inhibits synovial sarcoma by targeting GINS1: a novel downstream target oncogene in progression of synovial sarcoma

Tang, Lisa; Yu, Wenbin; Wang, Yihuan; Li, Hongtao; Shen, Zhiquan

doi:10.1007/s12094-019-02090-2

Cited by 40 publications

(31 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The environment was maintained with a 12-h light/dark cycle at 24 ± 2°C. A total of 100 μl of cellular suspension containing 1×10 7 PANC-1 or BxPC-3 cells or shNrf2 PANC-1 or BxPC-3 cells were injected subcutaneously into the right hind limbs of the mice. When the tumours grew tõ 50 mm 3 , the mice were randomly divided into four groups (n = 5) following simple randomization procedures: control group, shNrf2 group, anlotinib group and shNrf2 combined with anlotinib group.…”

Section: Xenograft Studiesmentioning

confidence: 99%

“…It was initially designed to inhibit vascular endothelial growth factor receptor (VEGFR) but is reported to affect other tumour proliferation-related receptor tyrosine kinases, including platelet-derived growth factor α and β, Ret, c-kit, fibroblast growth factor receptor (FGFR) and so forth 6 . Clinical trials of this drug in various cancers, such as sarcoma 7 , renal cell carcinoma 8 and colorectal tumours 9 , are also under development. Interestingly, compared with previous TKIs (sorafenib and sunitinib), favourable efficacy data for anlotinib in renal cancer patients were reported 8 .…”

Section: Introductionmentioning

confidence: 99%

“…To date, anlotinib has been proven to be effective in several types of carcinomas. In synovial sarcoma, anlotinib targets the GINS1 gene and inhibits tumour growth by promoting apoptosis 7 . In hepatocellular carcinoma, anlotinib also induces apoptosis and inhibits proliferation via downregulation of the Erk and Akt pathways 10 .…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Reactive oxygen species mediate anlotinib-induced apoptosis via activation of endoplasmic reticulum stress in pancreatic cancer

et al. 2020

View full text Add to dashboard Cite

Anlotinib (AL3818), a novel multi-targeted receptor tyrosine kinase inhibitor, has recently been proven to be an antitumour drug. This study aimed to explore the antitumour effect of anlotinib and its underlying molecular mechanisms in human pancreatic cancer (PC) cells. The anti-proliferative effect of anlotinib for three PC cell lines was validated using CCK-8, colony formation and EdU detection assays. Cell cycle, cell apoptosis, and reactive oxygen species (ROS) detection assays, a PC xenograft model and immunohistochemistry were performed to elucidate the mechanisms by which anlotinib induced tumour lethality in vitro and in vivo. These results demonstrated that anlotinib inhibited proliferation, induced G2/M phase arrest and triggered apoptosis in PC cell lines. Anlotinib induced PC’s apoptosis through the accumulation of ROS which activated the endoplasmic reticulum (ER) stress via PERK/p-eIF2α/ATF4 pathway. Furthermore, we demonstrated that the expression level of Nrf2, an antioxidant protein, increased with anlotinib treatment. Nrf2 knockdown enhanced the pro-apoptotic effect of anlotinib and the expression of the PERK/p-eIF2α/ATF4 pathway. The in vivo results suggested that suppressing Nrf2 improved the antitumour effect of anlotinib on PC cells. These data indicated that the apoptotic effect of anlotinib on PC cells was induced by ER stress via the accumulation of ROS. In the future, anlotinib combined with an Nrf2 inhibitor may provide a new therapeutic strategy for the treatment of human PC.

show abstract

Section: Xenograft Studiesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Reactive oxygen species mediate anlotinib-induced apoptosis via activation of endoplasmic reticulum stress in pancreatic cancer

et al. 2020

View full text Add to dashboard Cite

show abstract

“…GINS1 mRNA level is positively correlated with tumor size in CRC patients and is a prognostic marker of CRC [67]. This gene has been recently introduced as a targeted oncogenic agent for inhibition of synovial sarcoma meaning that expression inhibition of this gene promotes apoptosis [68]. It was upregulated in PvsN analysis, therefore, would be a potential target for inhibition of colorectal cancer progression by preventing initiation of DNA replication machinery.…”

Section: Discussionmentioning

confidence: 99%

Systems biomedicine of primary and metastatic colorectal cancer reveals potential therapeutic targets

Piran

Sepahi

et al. 2020

Preprint

View full text Add to dashboard Cite

Colorectal cancer is one of the leading causes of cancer death worldwide. Patient survival at the time of diagnosis depends largely on the stage of the tumor. Therefore, understanding the molecular mechanisms promoting cancer progression from early stages to high-grade stages is essential for therapeutic approaches. In the present study, we conducted transcriptomic data analysis employing a systems biology method to identify potential molecular targets for colorectal cancer treatment. These targets went under investigation one by one. We proposed some genes that their expression induction or suppression alone or in combination with each other would inhibit tumor progression or metastasis based on their biological activity. They are involved in cell proliferation, energy production under hypoxic conditions, epithelial to mesenchymal transition (EMT) and angiogenesis.Employing a network analysis viewpoint, some genes were discovered that has not been reported noticeably in any kind of cancer so far. As a result, they might have some roles in progression of colorectal cancer.

show abstract

“…For this reason, Anlotinib has been approved in China for the treatment of patients with advanced or metastatic non-small cell lung cancer 20 , and also is undergoing phase II and/or III clinical development for various sarcomas and carcinomas in China, USA and Italy 21 . Besides angiogenesis associated targets, new mechanisms and targets have been reported for Anlotinib inhibitory action on tumor growth 22,23 . Since Anlotinib can inactivate both AKT and ERK pathway, it is reasonable to assume that Anlotinib might also have a potential antileukemia activity.…”

mentioning

confidence: 99%

Anlotinib suppresses MLL-rearranged acute myeloid leukemia cell growth through inhibiting SETD1A/AKT-mediated DNA damage response

Chen

Feng

Fang

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Leukemias driven by chromosomal translocation of the mixed-lineage leukemia gene (MLL) are highly prevalent in hematological malignancy. The poor survival rate and lack of an effective targeted therapy for patients with MLL-rearranged (MLL-r) leukemias emphasize an urgent need for improved knowledge and novel therapeutic approaches for these malignancies. In this study, we investigated the potential effectiveness and mechanism of Anlotinib, a novel receptor tyrosine kinase inhibitor, in MLL-r acute myeloid leukemia(AML). Methods: MLL-r AML cell lines were treated with different concentration of Anlotinib, then cell viability, apoptosis and cell cycle were analyzed. Next, the anti-leukemia effect of Anlotinib was further evaluated in vivo in a xenograft model of AML-carrying MLL-rearrangement. Finally, we performed RNA-seq analysis, Gene Set Enrichment Analysis (GSEA) and western bolting to explore the underlying mechanism of the anti-leukemia effect of Anlotinib. Results: Our findings revealed that Anlotinib significantly suppresses the growth, promotes robust apoptosis and induces G2/M arrest in MLL-r AML cells. Moreover, Anlotinib effectively inhibited the growth of MLL-r AML cells in a xenograft murine model. In mechanism, we find that the inhibitive role of Anlotinib in MLL-r AML could be largely attributed to the dysfunction of DNA damage and repair. Furthermore, we confirmed that Anlotinib impaired DNA damage response via inhibiting SETD1A and AKT.

show abstract

Anlotinib inhibits synovial sarcoma by targeting GINS1: a novel downstream target oncogene in progression of synovial sarcoma

Cited by 40 publications

References 29 publications

Reactive oxygen species mediate anlotinib-induced apoptosis via activation of endoplasmic reticulum stress in pancreatic cancer

Reactive oxygen species mediate anlotinib-induced apoptosis via activation of endoplasmic reticulum stress in pancreatic cancer

Systems biomedicine of primary and metastatic colorectal cancer reveals potential therapeutic targets

Anlotinib suppresses MLL-rearranged acute myeloid leukemia cell growth through inhibiting SETD1A/AKT-mediated DNA damage response

Contact Info

Product

Resources

About