Inhibition of esophageal-carcinoma cell proliferation by genistein via suppression of JAK1/2-STAT3 and AKT/MDM2/p53 signaling pathways

Gao, Jing; Xia, Rongmu; Chen, Jianbo; Luo, Xianyang; Ke, Chunlin; Ren, Chen; Li, Jiayi; Mi, Yanjun

doi:10.18632/aging.103019

Cited by 41 publications

(26 citation statements)

References 50 publications

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“…It has also been reported that P53, a famous tumor suppressor gene, inhibits NSCLC cell proliferation, invasion and epithelial‐mesenchymal transition 47–49 . AKT also regulates the tumor characteristics of tumor by MDM2/p53 signal pathway 50–52 . Our results indicated that AKT/MDM2/p53 pathway participates in the protective effect of HAX1 in lung cancer.…”

Section: Discussionsupporting

confidence: 68%

HAX1 enhances the survival and metastasis of non‐small cell lung cancer through the AKT/mTOR and MDM2/p53 signaling pathway

et al. 2020

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Background HS‐1‐associated protein‐1 (HAX1) has been reported to be overexpressed in non‐small cell lung cancer (NSCLC) tissues. However, the underlying mechanism of HAX1 in NSCLC has not previously been demonstrated. The present study investigated the role and underlying mechanism of HAX1 in NSCLC. Methods The HAX1 expression were confirmed in NSCLC tissues through TCGA database and qRT‐PCR. Moreover, we performed qRT‐PCR, Western blotting, Transwell assays, TUNEL assays and so on to evaluate the role of HAX1 in A549 and H1299 cell lines. Results mRNA expression of HAX1 was overexpressed in NSCLC tissues compared to adjacent normal tissues according to The Cancer Genome Atlas (TCGA) database. QRT‐PCR assays showed that HAX1 mRNA expression was upregulated in NSCLC tissues. The high HAX1 mRNA levels were found to be positively associated with tumor size, TNM stage and lymphatic metastasis. Silencing of HAX1 promoted apoptosis and reduced invasion of A549 and H1299 cells by inhibiting the AKT/mTOR and MDM2/P53 signal pathway. AKT agonist SC79 could inhibit apoptosis and promote proliferation, migration and invasion of A549 and H1299 cells transfected with si‐HAX1. Conclusions The present study provided a better understanding of HAX1 mechanism in NSCLC and potential therapeutic target for NSCLC.

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Section: Discussionsupporting

confidence: 68%

HAX1 enhances the survival and metastasis of non‐small cell lung cancer through the AKT/mTOR and MDM2/p53 signaling pathway

et al. 2020

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“…A total of 261 co-expressed genes of NCAPG were identified by co-expression analysis, and pathway enrichment analysis indicated that these co-expressed genes were significantly enriched in the p53 signaling pathway. Numerous studies have demonstrated that the activation of the p53 signaling pathway is associated with the development of various types of cancer, including breast cancer ( 66 – 68 ). Furthermore, the association between NCAPG and p53 has been previously reported.…”

Section: Discussionmentioning

confidence: 99%

NCAPG upregulation mediated by four microRNAs combined with activation of the p53 signaling pathway is a predictor of poor prognosis in patients with breast cancer

Dong

Cui

et al. 2021

Oncol Lett

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The role of non-SMC condensin I complex subunit G (NCAPG) in breast cancer remains unclear. The present study used online databases, reverse transcription-quantitative PCR, flow cytometry and western blotting to determine the expression levels, prognosis and potential molecular mechanisms underlying the role of NCAPG in breast cancer. The association between NCAPG expression and several different clinicopathological parameters in patients with breast cancer was determined, and the results revealed that NCAPG expression was negatively associated with estrogen receptor and progesterone receptor positive status, but was positively associated with HER2 positive status, Nottingham Prognostic Index score and Scarff-Bloom-Richardson grade status. Furthermore, upregulated expression levels of NCAPG resulted in a poor prognosis in patients with breast cancer. A total of 27 microRNAs (miRNAs/miRs) were predicted to target NCAPG, among which four miRNAs (miR-101-3p, miR-195-5p, miR-214-3p and miR-944) were predicted to most likely regulate NCAPG expression in breast cancer. A total of 261 co-expressed genes of NCAPG were identified, including cell division cyclin 25 homolog C (CDC25C), and pathway enrichment analysis indicated that these co-expressed genes were significantly enriched in the p53 signaling pathway. CDC25C expression was downregulated in breast cancer and was associated with a poor prognosis. These findings suggested that upregulated NCAPG expression may be a prognostic biomarker of breast cancer.

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“…Our results showed that PL significantly reduced the expression of PI3K/AKT/mTOR at the protein level, therefore, we believe that PL may exert its cycle arrest and induce cell apoptosis through the PI3K/AKT/mTOR signaling pathway. AKT can promote the phosphorylation of MDM2 to inhibit the degradation of p53 [ 44 ], and AKT can directly inhibit the phosphorylation of p21 and p27 to achieve the purpose of cell cycle arrest [ 45 , 46 ]. In addition, AKT inhibits the phosphorylation of GSK-3β [ 47 ], GSK-3β further induced apoptosis [ 48 ], several researchers have revealed that PL shows its cell cycle arrest and apoptosis by inhibiting PI3K/AKT/mTOR in other cell lines [ 49 – 51 ].…”

Section: Discussionmentioning

confidence: 99%

Suppressive effects of plumbagin on the growth of human bladder cancer cells via PI3K/AKT/mTOR signaling pathways and EMT

et al. 2020

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Background Novel chemotherapeutic drugs with good anti-tumor activity are of pressing need for bladder cancer treatment. In this study, plumbagin (PL), a natural plant-derived drug extracted from Chinese herbals, was identified as a promising candidate for human bladder cancer (BCa) chemotherapy. Methods The anti-tumor activity of PL was evaluated using a series of in vitro experiments, such as MTT, transwell assay, flow cytometry, quantitative real-time PCR (qRT-PCR) and western blotting. We established xenograft tumors in nude mice by subcutaneous injection with the human bladder cancer T24 cells. Results The results showed that PL could inhibit the proliferation, migration and survival of BCa cells (T24 and UMUC3 cells) in a time- and dose-dependent way. We found PL promotes the cell cycle arrest and apoptosis by inhibiting PI3K/AKT/mTOR signaling pathway, which inhibits cell proliferation. In vivo, anti-tumor activity of PL was further investigated using a BCa cell xenograft mice model. To simulate clinical chemotherapy, the PL were intravenously injected with a dose of 10 mg/kg for 10 times. Compared with the blank control, the tumor weight in PL treated group decreased significantly from 0.57 ± 0.04 g to 0.21 ± 0.06 g (P < 0.001). Conclusions In our study. We found PL inhibits the proliferation of T24 and UMUC3 cells in vivo and in vitro, which may play a role through several downstream effectors of PI3K/AKT/mTOR signaling pathway to promote the cell cycle arrest and apoptosis. Meanwhile, we consider that PL may inhibit the migration of bladder cancer cells via EMT suppression and induce ROS generation to make cell apoptosis. This work screened out a novel chemotherapeutic drug (plumbagin) with relatively good anti-tumor activity, which possessed great potential in BCa chemotherapy.

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Inhibition of esophageal-carcinoma cell proliferation by genistein via suppression of JAK1/2-STAT3 and AKT/MDM2/p53 signaling pathways

Cited by 41 publications

References 50 publications

HAX1 enhances the survival and metastasis of non‐small cell lung cancer through the AKT/mTOR and MDM2/p53 signaling pathway

HAX1 enhances the survival and metastasis of non‐small cell lung cancer through the AKT/mTOR and MDM2/p53 signaling pathway

NCAPG upregulation mediated by four microRNAs combined with activation of the p53 signaling pathway is a predictor of poor prognosis in patients with breast cancer

Suppressive effects of plumbagin on the growth of human bladder cancer cells via PI3K/AKT/mTOR signaling pathways and EMT

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