20(S)-Protopanaxadiol-Induced Apoptosis in MCF-7 Breast Cancer Cell Line through the Inhibition of PI3K/AKT/mTOR Signaling Pathway

Zhang, Hong; Xu, Huali; Wang, Yu-Chen; Lu, Zeyuan; Yu, Xiaofeng; Sui, Dayun

doi:10.3390/ijms19041053

Cited by 37 publications

(30 citation statements)

References 30 publications

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“…The PI3K/Akt/mTOR signaling pathway has been reported to exert vital function in cell proliferation, differentiation, migration and invasion [31,32]. In our present study, we explored the correlation between SNHG20 and PI3K/Akt/mTOR signaling.…”

Section: Discussionmentioning

confidence: 92%

LncRNA SNHG20 promotes tumorigenesis and cancer stemness in glioblastoma via activating PI3K/Akt/mTOR signaling pathway

Gao¹,

He²,

Zhu³

et al. 2019

neo

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Long noncoding RNAs (lncRNAs) play crucial roles in the development of human cancers. LncRNA small nucleolar RNA host gene 20 (SNHG20) has been reported to be an oncogene in several cancers, whereas the specific role of SNHG20 in glioblastoma is unclear. In this study, we found that SNHG20 was significantly upregulated in glioblastoma tissues and cell lines. Survival analysis suggested that high expression of SNHG20 indicated the low overall survival rate of glioblastoma patients. Subsequently, gain or loss-of-function assays were carried out to examine the effect of SNHG20 on glioblastoma cell proliferation and apoptosis. We found that SNHG20 knockdown obviously suppressed cell proliferation, increased cell apoptosis and impaired stem properties, while SNHG20 overexpression led to the opposite results. In vivo experiment demonstrated that knockdown of SNHG20 efficiently suppressed cell growth in vivo. Furthermore, western blotting demonstrated that the PI3K/Akt/mTOR signaling pathway was activated by SNHG20 in glioblastoma cells. At last, rescue assays validated that PI3K/Akt/mTOR signaling pathway was involved in the glioblastoma progression mediated by SNHG20. Taken together, this study revealed that SNHG20 regulated PI3K/Akt/mTOR signaling pathway to promote tumorigenesis and stemness of glioblastoma.

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Section: Discussionmentioning

confidence: 92%

LncRNA SNHG20 promotes tumorigenesis and cancer stemness in glioblastoma via activating PI3K/Akt/mTOR signaling pathway

Gao¹,

He²,

Zhu³

et al. 2019

neo

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“…This pathway serves a vital role in regulating cell proliferation, apoptosis, differentiation and metabolism by affecting the activation state of several downstream effector molecules (26–28). In recent years, abnormal activation of the PI3K/Akt/mTOR pathway has been detected in numerous human malignant tumors, and activation of this pathway may be a critical factor leading to the proliferation and metastasis of tumor cells (29–31).…”

Section: Introductionmentioning

confidence: 99%

Inhibition of miR‑214 attenuates the migration and invasion of triple‑negative breast cancer cells

Zhang

Zhao

et al. 2019

Mol Med Report

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Triple-negative breast cancer (TNBC) is a subtype of breast cancer. MicroRNA (miR)-214 is closely associated with controlling the development of tumor cells; therefore, in the present study, the target gene and effects of miR-214 on TNBC cells were explored. Luciferase activity was examined by luciferase reporter assay. The viability, invasion and migration of MDA-MB-231 TNBC cells were measured using Cell Counting kit-8, Transwell and wound-healing assays, respectively. The expression levels of various factors were determined using reverse transcription-quantitative polymerase chain reaction and western blotting. The results demonstrated that the expression levels of miR-214 were higher and the levels of α1-antitrypsin (α1-AT) were lower in TNBC tissues compared with in normal tissues. Subsequently, α1-AT was revealed to be a target of miR-214. Furthermore, inhibition of miR-214 decreased cell viability, invasion and migration, enhanced the expression of E-cadherin and tissue inhibitor of metalloproteinases-2, and reduced the expression of metastatic tumour antigen 1 and matrix metalloproteinase-2. Inhibition of miR-214 also significantly downregulated the phosphorylation of protein kinase B (Akt) and mammalian target of rapamycin (mTOR), and markedly downregulated that of phosphoinositide 3-kinase (PI3K); however, the expression levels of total PI3K, Akt and mTOR remained stable in all groups. Taken together, these findings indicated that α1-AT may be a target of miR-214. Downregulation of miR-214 markedly suppressed the viability, migration and invasion of MDA-MB-231 cells, and inhibited the PI3K/Akt/mTOR pathway. These findings suggested that miR-214 targeting α1-AT may be a potential mechanism underlying TNBC development.

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“…Hence, the expression levels of p-PI3K (p85) [ 32 ], p-AKT (Ser473) [ 33 ], t-PI3K, t-AKT, and p-mTOR (Ser2448) [ 33 ] were investigated after 24 h treatment with AAP-H. As shown in Figure 3 , AAP-H treatment led to a dose-dependent reduction in the levels of p-AKT (Ser473), p-PI3K (p85), and p-mTOR (Ser2448), whereas t-AKT and t-PI3K levels remained unaltered compared to the nontreated group. Multiple signaling pathways operate and cross-talk inside cells; hence, when one pathway is stimulated, the levels of proteins related to that pathway, as well as other associated pathways, change concomitantly [ 34 ].…”

Section: Resultsmentioning

confidence: 99%

“…The expression of members of the PI3K/AKT/mTOR signaling pathway (p-AKT (Ser473), p-PI3K (p85) and p-mTOR (Ser2448)) in tumor tissue from nude mice was examined using immunocytochemistry assay [ 33 ]. As shown in Figure 7 , p-AKT (Ser473), p-PI3K (p85), and p-mTOR (Ser2448) were detected in the cytoplasm and nucleus of the tumors; however, no expression was observed in the negative control group, whereas strong expression was observed in the positive control group.…”

Section: Resultsmentioning

confidence: 99%

Inhibition of Prostate Cancer DU-145 Cells Proliferation by Anthopleura anjunae Oligopeptide (YVPGP) via PI3K/AKT/mTOR Signaling Pathway

Tang

Sun

et al. 2018

Marine Drugs

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We investigated the antitumor mechanism of Anthopleura anjunae oligopeptide (AAP-H, YVPGP) in prostate cancer DU-145 cells in vitro and in vivo. Results indicated that AAP-H was nontoxic and exhibited antitumor activities. Cell cycle analysis indicated that AAP-H may arrest DU-145 cells in the S phase. The role of the phosphatidylinositol 3-kinase/protein kinase B/mammalian rapamycin target protein (PI3K/AKT/mTOR) signaling pathway in the antitumor mechanism of APP-H was investigated. Results showed that AAP-H treatment led to dose-dependent reduction in the levels of p-AKT (Ser473), p-PI3K (p85), and p-mTOR (Ser2448), whereas t-AKT and t-PI3K levels remained unaltered compared to the untreated DU-145 cells. Inhibition of PI3K/AKT/mTOR signaling pathway in the DU-145 cells by employing inhibitor LY294002 (10 μM) or rapamycin (20 nM) effectively attenuated AAP-H-induced phosphorylation of AKT and mTOR. At the same time, inhibitor addition further elevated AAP-H-induced cleaved-caspase-3 levels. Furthermore, the effect of AAP-H on tumor growth and the role of the PI3K/AKT/mTOR signaling pathway in nude mouse model were also investigated. Immunohistochemical analysis showed that activated AKT, PI3K, and mTOR levels were reduced in DU-145 xenografts. Western blotting showed that AAP-H treatment resulted in dose-dependent reduction in p-AKT (Ser473), p-PI3K (p85), and p-mTOR (Ser2448) levels, whereas t-AKT and t-PI3K levels remained unaltered. Similarly, Bcl-xL levels decreased, whereas that of Bax increased after AAP-H treatment. AAP-H also increased initiator (caspase 8 and 9) and executor caspase (caspase 3 and 7) levels. Therefore, the antitumor mechanism of APP-H on DU-145 cells may involve regulation of the PI3K/AKT/mTOR signaling pathway, which eventually promotes apoptosis via mitochondrial and death receptor pathways. Thus, the hydrophobic oligopeptide (YVPGP) can be developed as an adjuvant for the prevention or treatment of prostate cancer in the future.

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20(S)-Protopanaxadiol-Induced Apoptosis in MCF-7 Breast Cancer Cell Line through the Inhibition of PI3K/AKT/mTOR Signaling Pathway

Cited by 37 publications

References 30 publications

LncRNA SNHG20 promotes tumorigenesis and cancer stemness in glioblastoma via activating PI3K/Akt/mTOR signaling pathway

LncRNA SNHG20 promotes tumorigenesis and cancer stemness in glioblastoma via activating PI3K/Akt/mTOR signaling pathway

Inhibition of miR‑214 attenuates the migration and invasion of triple‑negative breast cancer cells

Inhibition of Prostate Cancer DU-145 Cells Proliferation by Anthopleura anjunae Oligopeptide (YVPGP) via PI3K/AKT/mTOR Signaling Pathway

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