Crosstalk between PI3K and Ras pathways via protein phosphatase 2A in human ovarian clear cell carcinoma

Takai, Masaaki; Nakagawa, Takatoshi; Tanabe, Akiko; Ohmichi, Masahide; Asahi, Michio

doi:10.1080/15384047.2014.1002362

Cited by 12 publications

(11 citation statements)

References 38 publications

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“…In order to further demonstrate the suppression of ILQ on the PI3K/Akt/mTOR pathway, the human endometrial cancer cell line, Ishikawa, and ovarian cancer clear cell line, ES-2, were performed, as it has been reported that the PI3K/Akt/mTOR pathway may possibly be activated in these cells. 27 , 28 We observed similar results can be obtained by ILQ in Ishikawa and ES-2 cells. As shown in Figure 5 , ILQ significantly inhibited the phosphorylated form p-Akt and p-mTOR ( P <0.05) both in Ishikawa and ES-2 cells.…”

Section: Resultssupporting

confidence: 83%

“…The suppression of ILQ on the PI3K/Akt/mTOR pathway was further confirmed by the similar results obtained by ILQ in Ishikawa and ES-2 cells that the PI3K/Akt/mTOR pathway may possibly be activated. 27 , 28 Based on these results, ILQ has a significant suppression on the PI3K/Akt/mTOR pathway, which contributes to inhibit growth, metastasis, and survival of ovarian cancer. The inhibitory action of ILQ on PI3K/Akt/ mTOR pathway members is summarized in Figure 6 .…”

Section: Discussionmentioning

confidence: 98%

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Effects of isoliquiritigenin on ovarian cancer cells

Li¹,

Yang²,

Deng³

et al. 2018

OTT

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BackgroundOvarian cancer is one of the most fatal gynecologic malignancies, with most patients diagnosed at the late stage due to insidious onset and lack of early onset specific symptoms. Previous studies have implied that isoliquiritigenin (ILQ) is a promising chemopreventive agent against oral cancer.AimThis study aimed to investigate effects of ILQ and elucidate the related mechanism.Materials and methodsOvarian cancer cell lines, SKOV3 and OVCAR3, were treated with various concentrations of ILQ to detect the dose-dependent effects of ILQ and select the suitable concentration. CCK8 assay and clone formation efficiency assays were used to detect viability and proliferation. The cell migration, invasion, and apoptosis were evaluated by wound healing assays, transwell, and flow cytometry assays. The expression of apoptosis-related proteins (Caspase-3, Caspase3-p17, Bcl-2, Bax, and Bim) and related-signaling pathway proteins were also detected by Western blot.ResultsIt was observed that the treatment of ILQ inhibited the survival and proliferation of SKOV3 and OVCAR3 cells. ILQ treatment inhibited migration and invasion, and induced apoptosis in SKOV3 and OVCAR3 cells. Also, the ILQ treatment increased the Bax/Bcl-2 ratio in SKOV3 and OVCAR3 cells, suggesting that a mitochondrial apoptotic pathway was triggered. It was also observed that, after treated with ILQ, the phosphorylated form of Akt and mTOR decreased and the expression of GSK3β increased, while P70/S6K decreased. ILQ treatment also decreased the expression of Wnt3a and, therefore, caused the decrease of phosphorylated ERK. ILQ also suppressed the PI3K/Akt/mTOR pathway by reduced the expression level of p-Akt, p-mTOR, P70/S6K and Cyclin D1 in Ishikawa and ES-2 cells.ConclusionThe data suggested that ILQ inhibited viability, proliferation, and invasion, and induced apoptosis of SKOV3 and OVCAR3 cells through the PI3K/Akt/mTOR pathway. Together, the data revealed that ILQ treatment may be used as a novel strategy for ovarian cancer therapy.

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Section: Resultssupporting

confidence: 83%

Section: Discussionmentioning

confidence: 98%

Effects of isoliquiritigenin on ovarian cancer cells

Li¹,

Yang²,

Deng³

et al. 2018

OTT

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“…Anchorage‐dependent cell growth was measured spectrophotometrically using CCK‐8 (Wako Pure Chemical Industries) according to the manufacturer's instructions . Briefly, LoVo cells were plated onto a 96‐well plate at 2 × 10 5 cells/well and incubated overnight to allow cell attachment.…”

Section: Methodsmentioning

confidence: 99%

“…Anchorage-dependent cell growth was measured spectrophotometrically using CCK-8 (Wako Pure Chemical Industries) according to the manufacturer's instructions. (28,29) Briefly, LoVo cells were plated onto a 96-well plate at 2 9 10 5 cells/well and incubated overnight to allow cell attachment. The cells were then incubated with or without inhibitors for varying time periods (24 or 48 h) either in DMEM containing 10% FBS or in serum-free DMEM.…”

Section: Methodsmentioning

confidence: 99%

Augmented O‐GlcNAcylation of AMP‐activated kinase promotes the proliferation of LoVo cells, a colon cancer cell line

Ishimura

Nakagawa²,

Moriwaki³

et al. 2017

Cancer Science

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Increasing incidence of various cancers has been reported in diabetic patients. O‐linked N‐acetylglucosamine (O‐GlcNAc) modification of proteins at serine/threonine residues (O‐GlcNAcylation) is an essential post‐translational modification that is upregulated in diabetic patients and has been implicated in tumor growth. However, the mechanisms by which O‐GlcNAcylation promotes tumor growth remain unclear. Given that AMP‐activated kinase (AMPK) has been thought to play important roles in suppressing tumor growth, we evaluated the involvement of AMPK O‐GlcNAcylation on the growth of LoVo cells, a human colon cancer cell line. Results revealed that treatment with Thiamet G (TMG), an inhibitor of O‐GlcNAc hydrolase, increased both anchorage‐dependent and ‐independent growth of the cells. O‐GlcNAc transferase overexpression also increased the growth. These treatments increased AMPK O‐GlcNAcylation in a dose‐dependent manner, which led to reduced AMPK phosphorylation and mTOR activation. Chemical inhibition or activation of AMPK led to increased or decreased growth, respectively, which was consistent with the data with genetic inhibition of AMPK. In addition, TMG‐mediated acceleration of tumor growth was abolished by both chemical and genetic inhibition of AMPK. To examine the effects of AMPK O‐GlcNAcylation in vivo, the LoVo cells were s.c. transplanted onto the backs of BALB/c‐nu/nu mice. Injection of TMG promoted the growth and enhanced O‐GlcNAcylation of the tumors of the mice. Consistent with in vitro data, AMPK O‐GlcNAcylation was increased, which reduced AMPK phosphorylation and resulted in activation of mTOR. Collectively, the higher colon cancer risk of diabetic patients could be due to O‐GlcNAcylation‐mediated AMPK inactivation and subsequent activation of mTOR.

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“…Targeting these two pathways may be particularly effective in cancers attributed to mutations in PI3K and either KRAS or BRAF [108]. In ovarian clear cell carcinoma, inhibition of a downstream target of mTOR and HIF-1 activated the RAS pathway via MEK phosphorylation, and combination therapy using inhibitors of MEK and mTOR simultaneously synergistically eradicated HIF-1α-silenced cells [111].…”

Section: Simultaneously Targeting Major Oncogenic Pathways By Multiplmentioning

confidence: 99%

“Combo” nanomedicine: Co-delivery of multi-modal therapeutics for efficient, targeted, and safe cancer therapy

Kemp

Shim

Heo

et al. 2016

Advanced Drug Delivery Reviews

437

258

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a b s t r a c t a r t i c l e i n f oThe dynamic and versatile nature of diseases such as cancer has been a pivotal challenge for developing efficient and safe therapies. Cancer treatments using a single therapeutic agent often result in limited clinical outcomes due to tumor heterogeneity and drug resistance. Combination therapies using multiple therapeutic modalities can synergistically elevate anti-cancer activity while lowering doses of each agent, hence, reducing side effects. Co-administration of multiple therapeutic agents requires a delivery platform that can normalize pharmacokinetics and pharmacodynamics of the agents, prolong circulation, selectively accumulate, specifically bind to the target, and enable controlled release in target site. Nanomaterials, such as polymeric nanoparticles, gold nanoparticles/cages/shells, and carbon nanomaterials, have the desired properties, and they can mediate therapeutic effects different from those generated by small molecule drugs (e.g., gene therapy, photothermal therapy, photodynamic therapy, and radiotherapy). This review aims to provide an overview of developing multi-modal therapies using nanomaterials ("combo" nanomedicine) along with the rationale, up-to-date progress, further considerations, and the crucial roles of interdisciplinary approaches.

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Crosstalk between PI3K and Ras pathways via protein phosphatase 2A in human ovarian clear cell carcinoma

Cited by 12 publications

References 38 publications

Effects of isoliquiritigenin on ovarian cancer cells

Effects of isoliquiritigenin on ovarian cancer cells

Augmented O‐GlcNAcylation of AMP‐activated kinase promotes the proliferation of LoVo cells, a colon cancer cell line

“Combo” nanomedicine: Co-delivery of multi-modal therapeutics for efficient, targeted, and safe cancer therapy

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