Transcriptional inhibition by CDK7/9 inhibitor SNS-032 suppresses tumor growth and metastasis in esophageal squamous cell carcinoma

Zeng, Huishan; Yang, Huiru; Song, Yifan; Fang, Dong; Chen, Liang; Zhi-gang, Zhao; Wang, Chaojie; Xie, Songqiang

doi:10.1038/s41419-021-04344-w

Cited by 14 publications

(12 citation statements)

References 45 publications

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“…In this study, we found that SNS-032 significantly downregulated the expression levels of Bcl-2, XIAP, and Mcl-1 ( Figure 4 ). However, some previous studies on other cell types found that SNS-032 has no major effects on the protein levels of XIAP and Bcl-2 ( Zhang et al, 2019 ; Zeng et al, 2021 ). In our opinion, given that different cell lines undergo different transformations, the regulatory effects of SNS-032 may vary across different cell lines.…”

Section: Discussionmentioning

confidence: 89%

SNS-032 attenuates liver fibrosis by anti-active hepatic stellate cells via inhibition of cyclin dependent kinase 9

Chen

et al. 2022

Front. Pharmacol.

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Liver fibrosis is a common pathological process of all chronic liver diseases. Hepatic stellate cells (HSCs) play a central role in the development of liver fibrosis. Cyclin-dependent kinase 9 (CDK9) is a cell cycle kinase that regulates mRNA transcription and elongation. A CDK9 inhibitor SNS-032 has been reported to have good effects in anti-tumor. However, the role of SNS-032 in the development of liver fibrosis is unclear. In this study, SNS-032 was found to alleviate hepatic fibrosis by inhibiting the activation and inducing the apoptosis of active HSCs in carbon tetrachloride-induced model mice. In vitro, SNS-032 inhibited the activation and proliferation of active HSCs and induced the apoptosis of active HSCs by downregulating the expression of CDK9 and its downstream signal transductors, such phosphorylated RNA polymerase II and Bcl-2. CDK9 short hairpin RNA was transfected into active HSCs to further elucidate the mechanism of the above effects. Similar results were observed in active HSCs after CDK9 knockdown. In active HSCs with CDK9 knockdown, the expression levels of CDK9, phosphorylated RNA polymerase II, XIAP, Bcl-2, Mcl-1, and ɑ-SMA significantly decreased, whereas those of cleaved-PARP1 and Bax decreased prominently. These results indicated that SNS-032 is a potential drug and CDK9 might be a new prospective target for the treatment of liver fibrosis.

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Section: Discussionmentioning

confidence: 89%

SNS-032 attenuates liver fibrosis by anti-active hepatic stellate cells via inhibition of cyclin dependent kinase 9

Chen

et al. 2022

Front. Pharmacol.

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“…The wounded area was recorded using an inverted phase-contrast microscope. The wound-healing rate was calculated as: ([wound width at 0 h − width at 24 h]/width at 0 h) × 100% 16 .…”

Section: Methodsmentioning

confidence: 99%

CAMSAP2 promotes colorectal cancer cell migration and invasion through activation of JNK/c-Jun/MMP-1 signaling pathway

Wang

Liu

Ding

et al. 2022

Sci Rep

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CAMSAP2 has been reported to act as an oncogene in hepatocellular carcinoma. However, the expression CAMSAP2 and its potential roles in colorectal cancer remain unclear. In this study, qRT-PCR and immunoblotting analysis were used to detect the mRNA and protein levels of CAMSAP2 in colorectal cancer tissues and cell lines. Wound-healing, transwell migration and invasion assay were performed to determine whether CAMSAP2 promotes the capabilities of migration and invasion of colorectal cancer cells. The results showed that CAMSAP2 was highly elevated in colorectal cancer tissues and cell lines. Moreover, the high CAMSAP2 expression was positively correlated with tumor invasion depth, lymph node metastasis, distant metastasis, and the poor prognosis of colorectal cancer. Additionally, ectopic expression of CAMSAP2 in colorectal cancer cells promoted the migration and invasion in vitro and enhanced the lung metastasis in nude mice. Conversely, silencing CAMSAP2 resulted in an opposite phenomenon. By gain- and loss-of function experiments, we demonstrated that MMP-1 was a substantial downstream target of CAMSAP2, and it played a crucial role in regulating the migration and invasion induced by CAMSAP2 in colorectal cancer cells. Mechanistically, CAMSAP2 promoted the activation of JNK/c-Jun signaling pathway and subsequently upregulated the transcription activity of MMP-1. Taken together, our findings demonstrated that CAMSAP2 promoted colorectal cancer cell migration, invasion and metastasis through activation of JNK/c-Jun/MMP-1 signaling pathway, indicating CAMSAP2 is a promising therapeutic target for the treatment of metastatic colorectal cancer patients.

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“…The cells were treated with above method ( Measurement of Glucose Uptake ) for 48 h later, Western Blot was carried out according to the reference ( 22 ).…”

Section: Methodsmentioning

confidence: 99%

Effects of two triterpenoids from Nigella sativa seeds on insulin resistance of 3T3-L1 adipocytes

et al. 2022

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Insulin resistance (IR) is a physiological abnormality that occurs when insulin fails to activate the signal transduction pathway in target organs. It was found that supplementation of Nigella sativa seeds with oral antidiabetic medicines helps improve blood glucose control by enhanced β cells activity and alleviation of IR. However, the activities and related mechanisms of phytochemicals from N. sativa seeds have not been thoroughly explored. In this study, the effects of two triterpenoids, 3-O-[β-D-xylopyranose-(1→3)-α-L-rhamnose-(1→2)-α-L-arabinose]-28-O-[α-L-rhamnose-(1→4)-β-D-glucopyranose-L-(1→6)-β-D-glucopyranose]-hederagenin (Hxrarg) and 3-O-[β-D-xylopyranose-(1→3)-α-L-rhamnose-(1→2)-α-L-arabinose]-hederagenin (Hxra), on IR were studied by 3T3-L1 adipocytes model. The results demonstrated that Hxrarg and Hxra inhibited maturation of 3T3-L1 preadipocytes, dramatically stimulated glucose uptake of IR-3T3-L1 adipocytes, promoted transcription of IRS, AKT, PI-3K, and GLUT4 mRNA. Western Blot results suggested that Hxrarg and Hxra were able to markedly up-regulate expression of p-IRS, p-AKT, PI-3K, and GLUT4 proteins. These findings could provide a basic foundation for the continued development and application of N. sativa in medicine and functional foods.

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Transcriptional inhibition by CDK7/9 inhibitor SNS-032 suppresses tumor growth and metastasis in esophageal squamous cell carcinoma

Cited by 14 publications

References 45 publications

SNS-032 attenuates liver fibrosis by anti-active hepatic stellate cells via inhibition of cyclin dependent kinase 9

SNS-032 attenuates liver fibrosis by anti-active hepatic stellate cells via inhibition of cyclin dependent kinase 9

CAMSAP2 promotes colorectal cancer cell migration and invasion through activation of JNK/c-Jun/MMP-1 signaling pathway

Effects of two triterpenoids from Nigella sativa seeds on insulin resistance of 3T3-L1 adipocytes

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