PI3K/Akt/mTOR signaling pathway and targeted therapy for glioblastoma

Li, Xiaoman; Wu, Changjing; Chen, Nianci; Gu, Huadi; Yen, Allen; Cao, Liu; Wang, Enhua; Wang, Liang

doi:10.18632/oncotarget.7961

Cited by 408 publications

(320 citation statements)

References 90 publications

(74 reference statements)

Supporting

Mentioning

314

Contrasting

Unclassified

Order By: Relevance

“…Yuge et al [36] demonstrated that nicotine promoted tumorigenesis and induced chemoresistance by activating the PI3K/Akt/mTOR pathway in bladder carcinomas . Furthermore, Li et al [37] verified that the inhibition of the PI3K/Akt/mTOR pathway could be a promising targeted therapy for glioblastoma, which was the most malignant type of gliomas ; this finding was in accordance with our results.…”

Section: Discussionsupporting

confidence: 92%

Tanshinone IIA Affects Autophagy and Apoptosis of Glioma Cells by Inhibiting Phosphatidylinositol 3-Kinase/Akt/Mammalian Target of Rapamycin Signaling Pathway

Ding

Wang²,

Wang³

et al. 2016

Pharmacology

View full text Add to dashboard Cite

Objective: To test the effects of Tanshinone IIA (Tan IIA) on cell viability, cycle, apoptosis, and autophagy of human glioma cell U251 by regulating phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signal pathway. Methods: Tan IIA and PI3K agonist (740 Y-P) were used to treat glioma cells U251. MTT assay was used to assess cell viability and flow cytometry was used to detect cell apoptosis and cell cycle. The expressions of apoptosis-related proteins (Bcl-2 and Bax), autophagy-related proteins (LC3B and Beclin 1) and PI3K/Akt/mTOR signal pathway-associated proteins (p-PI3K, p-Akt and p-mTOR) were evaluated by Western blotting. Results: Tan IIA decreased the expression of p-PI3K and p-Akt proteins, inhibited cell viability and promoted apoptosis. Meanwhile, the expression of Bax increased, while the expression of Bcl-2 decreased. In addition, Tan IIA promoted autophagy in U251 glioma cells and raised the expression of LC3B and Beclin 1. However, 740 Y-P played a reversed role of Tan IIA in cell viability, cycle, apoptosis, and autophagy of U251 cells. Conclusion: Tan IIA could suppress the viability of U251 cells and induce cell apoptosis and autophagy, which might be related to the inhibition of the PI3K/Akt/mTOR signal pathway.

show abstract

Section: Discussionsupporting

confidence: 92%

Tanshinone IIA Affects Autophagy and Apoptosis of Glioma Cells by Inhibiting Phosphatidylinositol 3-Kinase/Akt/Mammalian Target of Rapamycin Signaling Pathway

Ding

Wang²,

Wang³

et al. 2016

Pharmacology

View full text Add to dashboard Cite

show abstract

“…colorectal cancer (CRC), melanoma, and breast cancer, no or little improvement in outcome has been attained for others (e.g. GBM and head and neck cancer) [37,38]. Innate as well as acquired resistance mechanisms along with spatial (i.e.…”

Section: Strategies For Arginine-deprivation Therapy -Experimental Apmentioning

confidence: 99%

Arginine-Depleting Enzymes – An Increasingly Recognized Treatment Strategy for Therapy-Refractory Malignancies

Riess

Shokraie

Classen

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

Arginine auxotrophy occurs in certain tumor types and is usually caused by the silencing of argininosuccinate synthetase 1 or arginine lyase genes. Such tumors are often associated with an intrinsic chemoresistance and thus a poor prognosis. Arginine auxotrophy however renders these tumors vulnerable to treatment with arginine-degrading enzymes. Among the most frequently applied arginine-degrading agents are bacterial arginine deiminases (ADI). The anti-cancerous effects of ADI derived from different bacteria were extensively studied in numerous preclinical cell culture and xenograft models. Mycoplasma-derived ADI-PEG20 is most commonly used and is currently under clinical investigation as a single agent therapeutic as well as in combination with different antineoplastic compounds. Mechanistically, ADI is capable of reducing metabolic activity in tumor cells, contributing to autophagy, senescence and apoptosis in arginine auxotrophic cells. Although clinical trials are promising, the resistance development upon initial treatment response is an increasing challenge. Furthermore, interference of ADI with the tumor microenvironment is poorly understood. In the present review, we outline recent experimental ADI-based treatment approaches and their translation into the clinic. Furthermore, we summarize new insights into the molecular mechanisms underlying the anti-cancer effects of ADI that might facilitate the refinement of ADI-based combination therapy approaches.

show abstract

“…For its elusive response to standard treatments, the development of novel therapeutic approaches for GBM remains indeed a pivotal step in the modern oncologic research. Protocols based on radionuclide therapy appear to be particularly promising for the GBM treatment [2,[4][5][6][7]. Experimental evidence has clearly demonstrated that cancer cells have a particularly high fractional content of copper inside the cytoplasmic and nuclear fraction compared to normal cells.…”

Section: Introductionmentioning

confidence: 99%

The SGK1 Kinase Inhibitor SI113 Sensitizes Theranostic Effects of the 64CuCl2 in Human Glioblastoma Multiforme Cells

Catalogna

Talarico

Dattilo

et al. 2017

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: The importance of copper in the metabolism of cancer cells has been widely studied in the last 20 years and a clear-cut association between copper levels and cancer deregulation has been established. Copper-64, emitting positrons and β-radiations, is indicated for the labeling of a large number of molecules suitable for radionuclide imaging as well as radionuclide therapy. Glioblastoma multiforme (GBM) is the CNS tumor with the worse prognosis, characterized by high number of recurrences and strong resistance to chemo-radio therapy, strongly affecting patients survival. We have recently discovered and studied the small molecule SI113, as inhibitor of SGK1, a serine/threonine protein kinase, that affects several neoplastic phenotypes and signaling cascades. The SI113-dependent SGK1 inhibition induces cell death, blocks proliferation, perturbs cell cycle progression and restores chemoradio sensibility by modulating SGK1-related substrates. In the present paper we aim to characterize the combined effects of 64 CuCl 2 and SI113 on human GBM cell lines with variable p53 expression. Methods: Cell viability, cell death and stress/authopagic related pathways were then analyzed by FACS and WB-based assays, after exposure to SI113 and/or 64 CuCl 2 . Results: We demonstrate here, that i) 64 CuCl 2 is able to induce a time and dose dependent modulation of cell viability (with different IC 50 values) in highly malignant gliomas and that the co-treatment with SI113 leads to ii) additive/synergistic effects in terms of cell death; iii) enhancement of the effects of ionizing radiations, probably by a TRC1 modulation; iv) modulation of the autophagic response. Conclusions: Evidence reported here underlines the therapeutic potential of the combined treatment with SI113 and 64 CuCl 2 in GBM cells.G. Catalogna and C. Talarico equally contributed to this work.

show abstract

PI3K/Akt/mTOR signaling pathway and targeted therapy for glioblastoma

Cited by 408 publications

References 90 publications

Tanshinone IIA Affects Autophagy and Apoptosis of Glioma Cells by Inhibiting Phosphatidylinositol 3-Kinase/Akt/Mammalian Target of Rapamycin Signaling Pathway

Tanshinone IIA Affects Autophagy and Apoptosis of Glioma Cells by Inhibiting Phosphatidylinositol 3-Kinase/Akt/Mammalian Target of Rapamycin Signaling Pathway

Arginine-Depleting Enzymes – An Increasingly Recognized Treatment Strategy for Therapy-Refractory Malignancies

The SGK1 Kinase Inhibitor SI113 Sensitizes Theranostic Effects of the 64CuCl2 in Human Glioblastoma Multiforme Cells

Contact Info

Product

Resources

About