INPP4B reverses docetaxel resistance and epithelial-to-mesenchymal transition via the PI3K/Akt signaling pathway in prostate cancer

Chen, Haiwen; Li, Hongliang; Chen, Qi

doi:10.1016/j.bbrc.2016.06.073

Cited by 24 publications

(17 citation statements)

References 36 publications

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“…It has been reported that the activation of PI3K/AKT signaling pathway followed by AKT phosphorylation plays a role in regulation of cell survival, apoptosis, and drug resistance. 25 To study the mechanisms of KLT on the reversal of MDR, we examined the expression and phosphorylation of PTEN, PI3K, and AKT in HepG2/ADM cells by Western blotting ( Figure 6A ). The marked phosphorylation of AKT and PI3K was decreased in HepG2/ADM cells treated with KLT.…”

Section: Resultsmentioning

confidence: 99%

Kanglaite reverses multidrug resistance of HCC by inducing apoptosis and cell cycle arrest via PI3K/AKT pathway

Yang¹,

Hou²,

Yu³

et al. 2018

OTT

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BackgroundMultidrug resistance (MDR) frequently contributes to the failure of chemotherapeutic treatments in patients diagnosed with hepatocellular carcinoma (HCC). Revealing the molecular mechanism of MDR is indispensable for the development of effective chemotherapeutic drugs.PurposeDue to the low-toxicity modulators to inhibit MDR, we considered that Kanglaite (KLT) is a potential agent for reversing MDR in HCC.Materials and MethodsBEL-7402/5-fluorouracil (5-FU) and HepG2/adriamycin (ADM) were analyzed for cell viability, colony formation assay, cell scratch assay, and cell cycle analysis and apoptosis assay by flow cytometry. The expression of PARP, caspase-3, Bax, Bcl-2, CDC25C, Cyclin B1 and phosphorylation of PTEN, PI3K, and AKT in HepG2/ADM cells were detected by western blotting.ResultsThe proliferation of drug-resistant cell lines BEL-7402/5-FU and HepG2/ADM pretreated with KLT was significantly inhibited when compared with drug alone. KLT could increase the accumulation of ADM in HepG2/ADM cells. In this study, we found that KLT treatment notably reduced cell viability, induced apoptosis and cell cycle arrest in human HepG2/ADM and BEL-7402/5-FU cells, and effectively reversed the MDR by p-glycoprotein (P-gp) inhibition. Moreover, KLT decreased the phosphorylation of AKT and PI3K in KLT-treated HepG2/ADM cells. These data together implied that KLT might reverse drug resistance in HCC by blocking the PI3K/AKT signaling.ConclusionWe demonstrated that KLT reversed MDR of human HCC by inducing apoptosis and cell cycle arrest via the PI3K/AKT signaling pathway.

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Section: Resultsmentioning

confidence: 99%

Kanglaite reverses multidrug resistance of HCC by inducing apoptosis and cell cycle arrest via PI3K/AKT pathway

Yang¹,

Hou²,

Yu³

et al. 2018

OTT

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“…INPP4B was believed to inhibit the activity of Akt through the turnover of PI(3,4)P, and several reports have demonstrated the interaction between INPP4B and Akt signalling . Akt transmits angiogenic and oncogenic signals and can directly induce angiogenesis .…”

Section: Resultsmentioning

confidence: 99%

“…INPP4B was believed to inhibit the activity of Akt through the turnover of PI(3,4)P, 6 and several reports have demonstrated the interaction between INPP4B and Akt signalling. 12,21,22 Akt transmits angiogenic and oncogenic signals and can directly induce angiogenesis. 23 In this study, the results of western blot showed that INPP4B overexpression in PC3 and DU145 cells significantly decreased the protein levels of p-Akt ( Figure 4B; P<.05), but the total protein levels of Akt was a little bit decreased and the difference was not statistically significant.…”

Section: Inpp4b Mediates Angiogenesis Through the Pi3k/akt Pathwaymentioning

confidence: 99%

INPP4B overexpression suppresses migration, invasion and angiogenesis of human prostate cancer cells

Chen

2017

Clin Exp Pharma Physio

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Inositol polyphosphate 4-phosphatase B (INPP4B) has been identified as a tumour suppressor in different human cancers. However, the role of INPP4B in the angiogenesis of human prostate cancer cells remains unclear. In this study, we first compared the expression of INPP4B between prostate cancer tissues and tumour-adjacent normal prostate tissues using immunohistochemistry. Then, we explored the role of INPP4B in prostate cancer progression via transfection of a Flag-INPP4B plasmid into PC3 and DU145 cells in vitro and in vivo. Our results showed that reduced INPP4B staining was significantly correlated with the tumour-node-metastasis stage. Moreover, transfection with Flag-INPP4B plasmid suppressed the migration and invasion of prostate cancer cells through inactivating the PI3K/Akt signalling pathway, at the same time decreased vascular endothelial growth factor secretion and suppressed human umbilical vein endothelial cells proliferation and tube formation. Futhermore, it was also found that INPP4B could inhibit tumour growth and angiogenesis in vivo. Altogether, our results supported that INPP4B acted as a tumour suppressor in human prostate cancer, and provided insights into development of a targeted therapy for this disease.

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“…Effects of EPS8L3 on the PI3K/AKT signaling pathway in liver cancer cells. Previous studies have reported that the Pi3K/aKT signaling pathway plays an important role in the cell survival (19,20); thus, the expression and phosphorylation of Pi3K and aKT was evaluated to further investigate the potential role of ePS8l3 in liver cancer. it was observed that the knockdown of EPS8L3 significantly reduced the levels of p-Pi3K and p-aKT in the HepG2 cell line, as indicated by the ratio of p-Pi3K/Pi3K and p-aKT/aKT ( Fig.…”

Section: Association Between Eps8l3 Expression Clinicopathological Fmentioning

confidence: 99%

Upregulation of EPS8L3 is associated with tumorigenesis and poor prognosis in patients with liver cancer

Wang

et al. 2019

Mol Med Report

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epidermal growth factor receptor kinase substrate 8 (ePS8) plays critical roles in a variety of solid tumors. However, the biologic functions and clinical significance of ePS8-like 3 (ePS8l3), an ePS8-related protein, in liver cancer remain unclear. To measure ePS8l3 expression in liver cancer cell lines, reverse transcription-quantitative Pcr and western blot analyses were performed. The correlation between 338 patients with liver cancer and various clinicopathological factors obtained from the oncomine database were evaluated using the χ 2 test. Survival of patients with different expression of ePS8l3 was determined using Kaplan-Meier survival analysis with a log rank test, and cox regression analysis was performed to estimate the prognostic significance of EPS8L3 expression. additionally, cell proliferation and migration were determined using cell counting Kit-8 and wound healing assays. The results revealed that ePS8l3 expression was significantly upregulated in liver cancer tissues and cell lines (P<0.01), and that the expression of ePS8l3 was closely associated with grade (P=0.024) and mortality (P=0.011). Furthermore, survival analysis suggested patients with high ePS8l3 expression exhibited shorter survival compared with those with low ePS8l3 expression. cox regression analysis indicated that ePS8l3 could be regarded as a prognostic biomarker in patients with liver cancer (hazard ratio, 1.58; 95% confidence interval, 1.085-2.301; P=0.017). Additionally, in vitro assays revealed that EPS8L3 depletion significantly inhibited liver cancer cell proliferation and migration, and reduced the levels of phosphorylated Pi3K and aKT in the Pi3K/aKT signaling pathway. collectively, the results of the present study, for the first time to the best of our knowledge, demonstrated that ePS8l3 serves as an oncogene in liver cancer development; therefore, ePS8l3 may be a valuable prognostic predictor for patients with liver cancer.

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INPP4B reverses docetaxel resistance and epithelial-to-mesenchymal transition via the PI3K/Akt signaling pathway in prostate cancer

Cited by 24 publications

References 36 publications

Kanglaite reverses multidrug resistance of HCC by inducing apoptosis and cell cycle arrest via PI3K/AKT pathway

Kanglaite reverses multidrug resistance of HCC by inducing apoptosis and cell cycle arrest via PI3K/AKT pathway

INPP4B overexpression suppresses migration, invasion and angiogenesis of human prostate cancer cells

Upregulation of EPS8L3 is associated with tumorigenesis and poor prognosis in patients with liver cancer

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