A polysaccharide from Huaier ameliorates cisplatin nephrotoxicity by decreasing oxidative stress and apoptosis via PI3K/AKT signaling

Fang, Liang; Zhang, Yongzhen; Wang, Qi; Zang, Yuanwei; Li, Zeyan; Duan, Zhichen; Ren, Juchao; Xu, Zhonghua

doi:10.1016/j.ijbiomac.2019.07.219

Cited by 43 publications

(22 citation statements)

References 33 publications

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“…There is mounting evidence suggesting that the PI3K/ AKT signaling pathway plays an indispensable role in the regulation of cellular features such as survival, proliferation, and apoptosis. 37 The research of Tian et al 38 shows the PI3K/AKT pathway is involved in lung cancer cell proliferation and apoptosis. Fang et al 37 reveal that PI3K/ AKT signaling pathway plays an important role in kidney cell apoptosis.…”

Section: Discussionmentioning

confidence: 99%

“…37 The research of Tian et al 38 shows the PI3K/AKT pathway is involved in lung cancer cell proliferation and apoptosis. Fang et al 37 reveal that PI3K/ AKT signaling pathway plays an important role in kidney cell apoptosis. Another research demonstrates that radiation could promote cancer cell survival through activating the PI3K/AKT pathway.…”

Section: Discussionmentioning

confidence: 99%

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<p>Downregulation of RAGE Inhibits Cell Proliferation and Induces Apoptosis via Regulation of PI3K/AKT Pathway in Cervical Squamous Cell Carcinoma</p>

Li¹,

Song²,

Zhou³

et al. 2020

OTT

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Aim: The receptor for advanced glycation endproducts (RAGE) expression has been reported to be implicated with cancer development. In this study, the role of RAGE in the regulation of cervical squamous cancer cell proliferation, apoptosis and the mechanism of RAGE involved in the biological behaviors were explored. Methods: The RAGE expression was overexpressed or downregulated by lentivirus transfection. The effect of RAGE expression on cell proliferation was explored by CCK-8, MTT, and BrdU assay, and the effect of RAGE on tumor development was confirmed by the xenograft mouse model along with the immunohistochemistry stain of proliferating cell nuclear antigen (PCNA). Apoptosis was investigated by flow cytometry and TUNEL assay. Western blotting was performed to investigate the expression of possible proteins, including Bax, Bcl-2, PI3K, p-PI3K, AKT, and p-AKT. Results: Overexpression of RAGE promoted proliferation of cervical squamous cancer cell and increased PCNA expression. In the meantime, RAGE overexpression inhibited cell apoptosis along with a decrease of Bax/Bcl-2 ratio, and induction of PI3K/AKT activation. The in vivo results showed that overexpression of RAGE enhanced tumor growth. Conversely, knockdown of RAGE exhibited opposed effects on cervical cancer cells and xenograft mouse model. Furthermore, RAGE inhibitor FPS-ZM1 effectively inhibited SiHa cell viability and PCNA expression, and increased cell apoptosis and Bax/Bcl-2 ratio. Moreover, PI3K inhibitor LY294002 effectively inhibited activation of PI3K and AKT, and further repressed RAGE overexpression-induced cell proliferation and apoptosis inhibition. Conclusion: RAGE promotes the growth ability of cervical squamous cell carcinoma by inducing PCNA expression and inhibiting cell apoptosis via inactivation of the PI3K/AKT pathway.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

<p>Downregulation of RAGE Inhibits Cell Proliferation and Induces Apoptosis via Regulation of PI3K/AKT Pathway in Cervical Squamous Cell Carcinoma</p>

Li¹,

Song²,

Zhou³

et al. 2020

OTT

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“…Controversial results were reported in the PI3K/Akt pathway in different experimental models of induced-kidney injury. Some researchers reported its activation in the injured kidney [37,38,39,41,42,43,44] while others reported its downregulation [5,45,46,47,48]. This may be explained by using different animal models, experimental conditions, duration, therapies, phosphorylation sites analyzed, and detection methods in addition to the early and late stages of renal diseases [11,49,50].…”

Section: Discussionmentioning

confidence: 99%

Ginkgo Biloba Extract Alleviates Methotrexate-Induced Renal Injury: New Impact on PI3K/Akt/mTOR Signaling and MALAT1 Expression

2019

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Renal injury induced by the chemotherapeutic agent methotrexate (MTX) is a serious adverse effect that has limited its use in the treatment of various clinical conditions. The antioxidant activity of Ginkgo biloba extract (GB) was reported to mitigate renal injury induced by MTX. Our research was conducted to examine the nephroprotective role of GB versus MTX-induced renal injury for the first time through its impact on the regulation of phosphatidylinositol 3-kinase/protein kinase B/ mammalian target of rapamycin (PI3K/Akt/mTOR) signaling together with the renal level of TGF-β mRNA and long non-coding RNA-metastasis-associated lung adenocarcinoma transcript-1 (MALAT1) expression. A group of adult rats was intraperitoneally (ip) injected with MTX 20 mg/kg as a single dose to induce kidney injury (MTX group). The other group of rats was orally administered with GB 60 mg/kg every day for 10 days (GB+ MTX group). The MTX increased the serum creatinine and urea levels, renal TGF-β mRNA and MALAT1 expression, in addition to dysregulation of the PI3K/Akt/mTOR signaling when compared with normal control rats that received saline only (NC group). Moreover, renal damage was reported histopathologically in the MTX group. The GB ameliorated the renal injury induced by MTX and reversed the changes of these biochemical analyses. The involvement of PI3K/Akt/mTOR signaling and downregulation of TGF-β mRNA and MALAT1 renal expressions were firstly reported in the nephroprotective molecular mechanism of GB versus MTX-induced renal injury.

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“…These findings suggest that the mTOR functions as a positive regulator of cell survival during cisplatin treatment of renal tubular cells (Gao et al, 2012). Huaier polysaccharide (HP-1), an extraction of Trametes robiniophila Murr, relieved the expression of oxidative stress, inflammation and mitochondrial dysfunction, thereby protecting against kidney injury in cisplatin-treated mice (Fang et al, 2019). In human proximal tubule epithelial cell line (HK-2), HP inhibited cell apoptosis and cell cycle arrest by reducing the expression of phosphatidylinositol 3-kinase (PI3K), AKT and mTOR during cisplatin treatment, resulting in attenuating cisplatin nephrotoxicity (Fang et al, 2019).…”

Section: Targeting Mtor For Therapy In Cisplatin Nephrotoxicitymentioning

confidence: 95%

“…Huaier polysaccharide (HP-1), an extraction of Trametes robiniophila Murr, relieved the expression of oxidative stress, inflammation and mitochondrial dysfunction, thereby protecting against kidney injury in cisplatin-treated mice (Fang et al, 2019). In human proximal tubule epithelial cell line (HK-2), HP inhibited cell apoptosis and cell cycle arrest by reducing the expression of phosphatidylinositol 3-kinase (PI3K), AKT and mTOR during cisplatin treatment, resulting in attenuating cisplatin nephrotoxicity (Fang et al, 2019). Chen et al (2020) indicated that the inhibition of the enhancer of zeste homolog 2 (EZH2) upregulated Deptor level, subsequently suppressed mTORC1 and mTORC2 activities, decreased HuR and Bcl-2 expression, leading to apoptosis in renal tubular cells during cisplatin treatment in NRK-52E cells.…”

Section: Targeting Mtor For Therapy In Cisplatin Nephrotoxicitymentioning

confidence: 99%

AMPK/mTOR Signaling in Autophagy Regulation During Cisplatin-Induced Acute Kidney Injury

et al. 2020

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Autophagy is a conserved, multistep pathway that degrades and recycles dysfunctional organelles and macromolecules to maintain cellular homeostasis. Mammalian target of rapamycin (mTOR) and adenosine-monophosphate activated-protein kinase (AMPK) are major negative and positive regulators of autophagy, respectively. In cisplatin-induced acute kidney injury (AKI) or nephrotoxicity, autophagy is rapidly induced in renal tubular epithelial cells and acts as a cytoprotective mechanism for cell survival. Both mTOR and AMPK have been implicated in the regulation of autophagy in cisplatin-induced AKI. Targeting mTOR and/or AMPK may offer effective strategies for kidney protection during cisplatin-mediated chemotherapy.

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A polysaccharide from Huaier ameliorates cisplatin nephrotoxicity by decreasing oxidative stress and apoptosis via PI3K/AKT signaling

Cited by 43 publications

References 33 publications

<p>Downregulation of RAGE Inhibits Cell Proliferation and Induces Apoptosis via Regulation of PI3K/AKT Pathway in Cervical Squamous Cell Carcinoma</p>

<p>Downregulation of RAGE Inhibits Cell Proliferation and Induces Apoptosis via Regulation of PI3K/AKT Pathway in Cervical Squamous Cell Carcinoma</p>

Ginkgo Biloba Extract Alleviates Methotrexate-Induced Renal Injury: New Impact on PI3K/Akt/mTOR Signaling and MALAT1 Expression

AMPK/mTOR Signaling in Autophagy Regulation During Cisplatin-Induced Acute Kidney Injury

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