Salinomycin inhibits breast cancer progression via targeting HIF-1α/VEGF mediated tumor angiogenesis in vitro and in vivo

Dewangan, Jayant; Srivastava, Sonal; Mishra, Sakshi; Divakar, Aman; Kumar, Sadan; Rath, Srikanta Kumar

doi:10.1016/j.bcp.2019.04.026

Cited by 51 publications

(26 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Hif-1α was involved in the effects of propofol and TNF-α on VEGF, VEGFR-2, ERK and occludin in hCMEC/D3 cells It has been reported that VEGF could be regulated by Hif-1α [21]. As shown in Fig.…”

Section: Vegf/ Vegfr-2 Signaling Pathway Was Involved In the Effects mentioning

confidence: 83%

Propofol attenuated TNF-α-modulated occludin expression by inhibiting Hif-1α/ VEGF/ VEGFR-2/ ERK signaling pathway in hCMEC/D3 cells

et al. 2019

View full text Add to dashboard Cite

Background: The levels of tight junction proteins (TJs), especially occludin, correlate with blood-brain barrier (BBB) disruption caused by inflammation in central nervous system (CNS). It has been reported that propofol, the most commonly used anesthetic, could inhibit inflammation response in CNS. In this study, we investigated the effects of tumor necrosis factor-α (TNF-α) and propofol on occludin expression in human cerebral microvascular endothelial cell line, D3 clone (hCMEC/D3 cells), and explored the underlying mechanisms. Methods: The hCMEC/D3 cells were treated with propofol, followed by TNF-α. The expression and phosphorylation of Hif-1α, VEGF, VEGFR-2, ERK, p38MAPK and occludin were measured by Western blot analysis. The cell viability of hCMEC/D3 cells was measured by cell counting kit-8. Results: TNF-α (10 ng/ml, 4 h) significantly decreased the expression of occludin, which was attenuated by propofol (25 μM). TNF-α induced Hif-1α/VEGF/VEGFR-2/ERK signaling pathway, while propofol could inhibit it. TNF-α induced the phosphorylation of p38MAPK, while propofol had no effect on it. In addition, the inhibitors of Hif-1α, VEGFR-2, and ERK could reduce the effect of TNF-α on occludin expression. Conclusion: TNF-α could decrease the expression of occludin via activating Hif-1α/ VEGF/ VEGFR-2/ ERK signaling pathway, which was attenuated by propofol.

show abstract

Section: Vegf/ Vegfr-2 Signaling Pathway Was Involved In the Effects mentioning

confidence: 83%

Propofol attenuated TNF-α-modulated occludin expression by inhibiting Hif-1α/ VEGF/ VEGFR-2/ ERK signaling pathway in hCMEC/D3 cells

et al. 2019

View full text Add to dashboard Cite

show abstract

“…However, in a hypoxic environment, the levels of ubiquitin and hydroxylation are decreased, and the degradation of HIF-1α is inhibited. HIF-1α binds to HIF-1β to form a stable heterogeneous dimer structure and then transfers from the cytoplasm to the nucleus and binds to the hypoxia response element (HRE) on target genes such as EPO and VEGF to initiate the transcription process 27,28 .…”

Section: Discussionmentioning

confidence: 99%

Effect of mandibular advancement device treatment on HIF-1α, EPO and VEGF in the myocardium of obstructive sleep apnea–hypopnea syndrome rabbits

Zhu

Kang

Zhang

et al. 2020

Sci Rep

View full text Add to dashboard Cite

All methods in this study were performed in accordance with the medical ethics committee in Hospital of Stomatology, Hebei Medical University. Animal use and care was in accordance with the guidelines of the medical ethics committee for the housing and care of animals bred, supplied and used for scientific purposes. All experiments were performed in accordance with relevant guidelines and regulations. The work was approved by the medical ethics committee in Hospital of Stomatology, Hebei Medical University (Certificate No. [2017]016). Animal model development. Every effort was made to minimize animal pain and suffering. A total of 18 male 6-month-old New Zealand white rabbits (initial weight, 3-3.5 kg) were randomly divided into three groups: the OSHAS, MAD, and control groups, with 6 rabbits in each group. All of the animals were housed under normal laboratory conditions. Food and water were available ad libitum. The animal models were developed in the same way as in our previous studies 12,13. Briefly, OSAHS was induced via injection of gel into the submucous muscular layer in the centre of the soft palate 1.5 cm away from the junction of the soft and hard palate (Fig. 1). No gel was injected in the control group. Animals in these two groups were later confirmed to have OSAHS by clinical signs, CBCT scanning and polysomnography (PSG).

show abstract

“…VEGFA may mediate SERPINE1 in promoting PTX resistance. Since concomitant increases in VEGFA and SERPINE1 were detected in PTX-resistant BC cell lines, and given the central role of VEGFA in promoting tumor angiogenesis and growth (23)(24)(25), it was hypothesized that SERPINE1 may promote PTX resistance through induction of VEGFA.…”

Section: Knockdown Of Serpine1 Suppresses the Tumorigenic Capacity Ofmentioning

confidence: 99%

Knockdown of SERPINE1 reverses resistance of triple‑negative breast cancer to paclitaxel via suppression of VEGFA

Zhang

Jiang

2020

Oncol Rep

View full text Add to dashboard Cite

Breast cancer (BC) has a poor prognosis and a high number of visceral metastases. Serine protease inhibitor, clade E member 1 (SERPINE1) is a molecule involved in several human malignancies. However, it remains unknown if SERPINE1 plays a role in the development of taxane resistance in TNBC cells. In the present study, the role and mechanism of SERPINE1 in the development of paclitaxel (PTX) resistance in TNBC cells were investigated. A bioinformatics analysis of gene expression profiles in PTX-resistant cells indicated that SERPINE1 was significantly associated with PTX resistance. Furthermore, the levels of SERPINE1 mRNA and protein were higher in PTX-resistant cells with respect to those in PTX-sensitive parent cells. Knockdown of SERPINE1 significantly inhibited cell survival and induced cell apoptosis in vitro. In addition, SERPINE1 silencing led to downregulation of the key angiogenetic vascular endothelial growth factor A (VEGFA). Furthermore, suppression of SERPINE1 markedly attenuated tumor growth in vivo. Collectively, these findings indicated that SERPINE1 significantly contributed to the proliferation and apoptosis of TNBC cells by regulating VEGFA expression. The present study demonstrated SERPINE1 as an oncogene in PTX drug resistance of breast cancer, and revealed that it may serve as a possible target for treating BC.

show abstract

Salinomycin inhibits breast cancer progression via targeting HIF-1α/VEGF mediated tumor angiogenesis in vitro and in vivo

Cited by 51 publications

References 33 publications

Propofol attenuated TNF-α-modulated occludin expression by inhibiting Hif-1α/ VEGF/ VEGFR-2/ ERK signaling pathway in hCMEC/D3 cells

Propofol attenuated TNF-α-modulated occludin expression by inhibiting Hif-1α/ VEGF/ VEGFR-2/ ERK signaling pathway in hCMEC/D3 cells

Effect of mandibular advancement device treatment on HIF-1α, EPO and VEGF in the myocardium of obstructive sleep apnea–hypopnea syndrome rabbits

Knockdown of SERPINE1 reverses resistance of triple‑negative breast cancer to paclitaxel via suppression of VEGFA

Contact Info

Product

Resources

About