Targeting the PI3K/PTEN/AKT/mTOR Pathway in Treatment of Sarcoma Cell Lines

Lim, Hui Jun; Wang, Xiaochun; Crowe, Philip; Goldstein, David; Yang, Jialin

doi:10.21873/anticanres.11160

Cited by 25 publications

(18 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Musculoskeletal sarcomas, including OS, commonly develop aberrant activation of the PI3K/Akt signaling pathway [24]. Moreover, targeting the PI3K/Akt signaling pathway can be an approach for the treatment of sarcomas [25]. Zhang et al [26] also found that inhibiting the PI3K/Akt pathway suppressed the progression of Ewing sarcoma.…”

Section: Discussionmentioning

confidence: 99%

PENK inhibits osteosarcoma cell migration by activating the PI3K/Akt signaling pathway

Zhang

et al. 2020

J Orthop Surg Res

View full text Add to dashboard Cite

Background: This article reports the effects of proenkephalin (PENK) on osteosarcoma (OS) cell migration. Methods: A Gene Expression Omnibus (GEO) dataset was used to identify differentially expressed genes (DEGs) in OS tumor samples and normal human osteoblasts. Tumor tissue and adjacent normal tissue were collected from 40 OS patients. MG63 cells were transfected with si-PENK. Transwell migration assays and wound healing assays were performed to compare the effect of PENK on migration. Moreover, LY294002 was used to identify the potential mechanism. Gene expression was examined via qRT-PCR and Western blotting. Results: Bioinformatic analysis revealed that PENK was downregulated in OS tumor samples compared with normal human osteoblasts. Moreover, PENK was identified as the hub gene of the DEGs. The PI3K/Akt signaling pathway was significantly enriched in the DEGs. Moreover, PENK was downregulated in OS and MG63 cells compared with the corresponding control cells. Silencing PENK promoted MG63 cell migration; however, treatment with LY294002 partially attenuated PENK silencing-induced OS cell migration. Conclusion: PENK inhibits OS cell migration by activating the PI3K/Akt signaling pathway.

show abstract

Section: Discussionmentioning

confidence: 99%

PENK inhibits osteosarcoma cell migration by activating the PI3K/Akt signaling pathway

Zhang

et al. 2020

J Orthop Surg Res

View full text Add to dashboard Cite

show abstract

“…Components of the PI3K/Akt/mTOR signaling pathway are commonly upregulated in malignant tumors, and increased Akt phosphorylation is commonly observed ( 19 ). The activation of Akt signaling is associated with cell proliferation, migration and invasion ( 20 ).…”

Section: Discussionmentioning

confidence: 99%

Na+/H+ exchanger regulatory factor 1 overexpression suppresses the malignant phenotype of MIAPaCa-2 pancreatic adenocarcinoma cells by downregulating Akt phosphorylation

Zhang

Liu

2018

Oncol Lett

View full text Add to dashboard Cite

Na+/H+ exchanger regulatory factor 1 (NHERF1) is reported to be associated with the development of numerous types of tumor; however, its effects on the metastasis of pancreatic adenocarcinoma are not fully understood. In the present study, it was revealed that the expression level of NHERF1 in pancreatic adenocarcinoma is decreased compared with normal pancreatic tissue based on the analysis of a protein expression database. The present study was undertaken in order to investigate the potential effects of NHERF1 overexpression on the malignant phenotype of MIAPaCa-2 pancreatic adenocarcinoma cells. NHERF1 was stably overexpressed in this cell line, and Cell Counting Kit-8, wound healing and Transwell assays were used to detect the proliferative and migratory abilities of the cells. NHERF1 overexpression suppressed proliferation in the MIAPaCa-2 cell line compared with empty vector-transfected (negative control) cells. Additionally, NHERF1 overexpression significantly inhibited the migration of MIAPaCa-2 cells. The results of a western blot analysis identified that NHERF1 overexpression markedly decreased the expression of phosphorylated-protein kinase B (p-Akt), while no significant difference was observed between untransfected and negative control cells. Taken together, these results suggested that NHERF1 may be able to inhibit the proliferation and migration and alter the malignant phenotype of pancreatic adenocarcinoma cells via reduction of p-Akt levels. These findings indicate a potential novel approach to the treatment of pancreatic adenocarcinoma.

show abstract

“…Ligand binding initiates several signalling cascades involving cell growth, proliferation, apoptosis and autophagy [10,11] (Figure 1). The major signal transduction pathways are: ras/raf/mitogen activated protein kinase (MAPK), phosphoinositide 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) and Janus kinase/signal transducer and activator of transcription (JAK/STAT) [12][13][14][15], all of which promote cell survival [16]. We and others have reported that EGFR was overexpressed in many types of osteosarcomas and STSs [9,11,17].…”

Section: Research Papermentioning

confidence: 99%

“…An extensively studied downstream pathway of EGFR is the PI3K/AKT/ mTOR pathway, critically involved in the regulation of cell apoptosis [27], autophagy [10], proliferation [12,28] and metabolism [29]. Dysregulation of this pathway plays a major role in many different cancers [30,31].…”

Section: Research Papermentioning

confidence: 99%

The synergistic inhibitory effect of combining therapies targeting EGFR and mitochondria in sarcomas

et al. 2020

Self Cite

View full text Add to dashboard Cite

Our group previously demonstrated that sarcoma cell lines were insensitive to epidermal growth factor receptor (EGFR) inhibitor gefitinib monotherapy. PENAO, an anti-tumour metabolic compound created in our laboratory, is currently in clinical trials. Considering the positive regulation of tumour energy production by both the EGFR signalling and tumour metabolism pathways, this study aimed to investigate the effect and mechanisms of combination therapy using gefitinib and PENAO in sarcoma cell lines in vitro and in vivo. PENAO monotherapy reduced proliferation in 12 sarcoma cell lines. Combining gefitinib and PENAO resulted in synergistic inhibition in both a time-and dosedependent manner in 3 sarcoma cell lines with less prominent monotherapy effects. Combined treatment significantly enhanced cell death and perturbed mitochondrial function. In vivo combination therapy with PENAO and gefitinib was non-toxic to mice and significantly delayed tumour growth and prolonged survival. At 20 days after treatment, tumours from the combination treated mice were significantly smaller than those from untreated and single drug treated mice. The survival curves also showed significant difference across and between groups. The combination of PENAO and gefitinib in vitro and in vivo, shows promise as a treatment pathway in this poor outcome tumour.

show abstract

Targeting the PI3K/PTEN/AKT/mTOR Pathway in Treatment of Sarcoma Cell Lines

Abstract: Abstract. Background

Cited by 25 publications

References 30 publications

PENK inhibits osteosarcoma cell migration by activating the PI3K/Akt signaling pathway

PENK inhibits osteosarcoma cell migration by activating the PI3K/Akt signaling pathway

Na+/H+ exchanger regulatory factor 1 overexpression suppresses the malignant phenotype of MIAPaCa-2 pancreatic adenocarcinoma cells by downregulating Akt phosphorylation

The synergistic inhibitory effect of combining therapies targeting EGFR and mitochondria in sarcomas

Contact Info

Product

Resources

About