Stellettin B Induces G1 Arrest, Apoptosis and Autophagy in Human Non-small Cell Lung Cancer A549 Cells via Blocking PI3K/Akt/mTOR Pathway

Wang, Ran; Zhang, Qian; Peng, Xin; Zhou, Chang; Zhong, Yuxu; Chen, Xi; Qiu, Yuling; Jin, Meihua; Gong, Min; Kong, Dexin

doi:10.1038/srep27071

Cited by 129 publications

(127 citation statements)

References 38 publications

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“…Even more interesting is that the PI3K/AKT signaling pathway cause drug resistance by mediating tumor cells escape from apoptosis. 37, 38 Given the critical role of the PI3K/AKT signaling pathway in tumor cell drug resistance, we investigated whether ASIC1a mediated calcium influx to regulate the PI3K/AKT signaling pathway. Western blot analysis showed that the levels of PI3K and the phosphorylation of AKT were decreased in Bel7402/FU and HepG2/ADM cells treated with ASIC1a shRNA (Figure 8).…”

Section: Resultsmentioning

confidence: 99%

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ASIC1a mediates the drug resistance of human hepatocellular carcinoma via the Ca2+/PI3-kinase/AKT signaling pathway

Zhang

et al. 2017

Laboratory Investigation

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Chemotherapy is the main treatment method of patients with advanced liver cancer. However, drug resistance is a serious problem in the treatment of hepatocellular carcinoma (HCC). Acid sensing ion channel 1a (ASIC1a) is a H+-gated cation channel; it mediates tumor cell migration and invasion, which suggests that it is involved in the development of malignant tumors. Therefore, we studied the relationship between ASIC1a and drug resistance in human hepatocellular carcinoma. In our study, we found that ASIC1a is highly expressed in human HCC tissue, and that its levels were significantly increased in resistant HCC cells Bel7402/FU and HepG2/ADM. Inhibiting the activity of ASIC1a enhances the chemosensitivity of Bel7402/FU and HepG2/ADM cells. The overexpression of ASIC1a contributed to drug resistance in Bel7402 and HepG2 cells, whereas knockdown of ASIC1a overcame drug resistance in Bel7402/FU and HepG2/ADM cells. We further demonstrated that ASIC1a mediated calcium influx, which resulted in the activation of PI3K/AKT signaling and increased drug resistance. These data suggest that ASIC1a/Ca2+/PI3K/AKT signaling represents a novel pathway that regulates drug resistance, thus offering a potential target for chemotherapy of HCC.

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Section: Resultsmentioning

confidence: 99%

“…33, 34, 35, 36 As is known to all, PI3K/AKT pathway caused drug resistance, through which mediated tumor cells escape apoptosis. 37, 38 In cancer cells, whether Ca 2+ involved in drug resistance via the regulation of PI3K/AKT pathway is still unknown.…”

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confidence: 99%

ASIC1a mediates the drug resistance of human hepatocellular carcinoma via the Ca2+/PI3-kinase/AKT signaling pathway

Zhang

et al. 2017

Laboratory Investigation

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“…To analyse autophagic flux, LX‐2 cells were transfected with a tandem fluorescent mRFP‐GFP‐tagged LC3 plasmid 24 using Lipofectamine 2000. The expression of GFP and mRFP was visualized with Olympus FV1000 laser scanning confocal microscope (Olympus, Tokyo, Japan).…”

Section: Methodsmentioning

confidence: 99%

MicroRNA‐30a ameliorates hepatic fibrosis by inhibiting Beclin1‐mediated autophagy

Chen

et al. 2017

J Cellular Molecular Medi

100

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We explored the role of microRNA‐30a (miR‐30a) and the mechanism involved in hepatic fibrosis. MiR‐30a overexpression was achieved by miR‐30a mimics transfection in hepatic stellate cells (HSCs) (HSC‐T6, LX‐2), and miR‐30a agomir (ago‐miR‐30a) treatment in mice. MiR‐30a levels were measured using TaqMan miRNA assay system, and the localization of miR‐30a was detected by fluorescence in situ hybridization (FISH). The interaction of miR‐30a and Beclin1 was confirmed by dual‐luciferase reporter assay. Autophagic flux was analysed using tandem mRFP‐GFP‐LC3 fluorescence microscopy, electron microscopy and Western blot of LC3‐II/I ratio. MiR‐30a was notably down‐regulated in activated HSCs and LX‐2‐exosomes induced by TGF‐β1; overexpression of miR‐30a down‐regulated extracellular matrix (ECM), such as α‐SMA, TIMP‐1, and Collagen I expression, and suppressed cell viability in HSCs. MiR‐30a was significantly down‐regulated in hepatic fibrosis mice and overexpression of miR‐30a prevented BDL‐induced fibrogenesis, concomitant with the down‐regulation of ECM. MiR‐30a inhibited HSCs autophagy and increased lipid accumulation in HSCs and in mice fibrotic hepatic tissues. MiR‐30a inhibited its downstream effector of Beclin1 by direct targeting its 3′‐UTR region. Moreover, Knock‐down of Beclin1 by small interfering RNA (siRNA) inhibited HSC autophagy and activation in LX‐2 cells. In conclusion, miR‐30a is down‐regulated in hepatic fibrosis models and its overexpression prevents liver fibrogenesis by directly suppressing Beclin1‐mediated autophagy; therefore, miR‐30a may be a new potential therapeutic target for controlling hepatic fibrosis.

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“…63 Briefly, treated cells were harvested, washed with PBS, and stained with 20 μ M DCFH-DA (Applygen Technologies, Beijing, China) for 20 min at 37 °C in the dark. Fluorescent signals were detected with a FACS Verse flow cytometer (BD, Germany).…”

Section: Methodsmentioning

confidence: 99%

Berberine-sonodynamic therapy induces autophagy and lipid unloading in macrophage

et al. 2017

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Impaired autophagy in macrophages accompanies the progression of atherosclerosis and contributes to lipid loading in plaques and ineffective lipid degradation. Therefore, evoking autophagy and its associated cholesterol efflux may provide a therapeutic treatment for atherosclerosis. In the present study, berberine-mediated sonodynamic therapy (BBR-SDT) was used to induce autophagy and cholesterol efflux in THP-1 macrophages and derived foam cells. Following BBR-SDT, autophagy was increased in the macrophages, autophagy resistance in the foam cells was prevented, and cholesterol efflux was induced. The first two effects were blocked by the reactive oxygen species scavenger, N-acetyl cysteine. BBR-SDT also reduced the phosphorylation of Akt and mTOR, two key molecules in the PI3K/AKT/mTOR signaling pathway, which is responsible for inducing autophagy. Correspondingly, treatment with the autophagy inhibitor, 3-methyladenine, or the PI3K inhibitor, LY294002, abolished the autophagy-induced effects of BBR-SDT. Furthermore, induction of cholesterol efflux by BBR-SDT was reversed by an inhibition of autophagy by 3-methyladenine or by a small interfering RNA targeting Atg5. Taken together, these results demonstrate that BBR-SDT effectively promotes cholesterol efflux by increasing reactive oxygen species generation, and this subsequently induces autophagy via the PI3K/AKT/mTOR signaling pathway in both ‘normal' macrophages and lipid-loaded macrophages (foam cells). Thus, BBR-SDT may be a promising atheroprotective therapy to inhibit the progression of atherosclerosis and should be further studied.

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Stellettin B Induces G1 Arrest, Apoptosis and Autophagy in Human Non-small Cell Lung Cancer A549 Cells via Blocking PI3K/Akt/mTOR Pathway

Cited by 129 publications

References 38 publications

ASIC1a mediates the drug resistance of human hepatocellular carcinoma via the Ca2+/PI3-kinase/AKT signaling pathway

ASIC1a mediates the drug resistance of human hepatocellular carcinoma via the Ca2+/PI3-kinase/AKT signaling pathway

MicroRNA‐30a ameliorates hepatic fibrosis by inhibiting Beclin1‐mediated autophagy

Berberine-sonodynamic therapy induces autophagy and lipid unloading in macrophage

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