EG-VEGF silencing inhibits cell proliferation and promotes cell apoptosis in pancreatic carcinoma via PI3K/AKT/mTOR signaling pathway

Liver cancer is one of the most common and lethal cancers in human digestive system, which kills more than half a million people every year worldwide. This study aimed to investigate the effects of kaempferol, a flavonoid compound isolated from vegetables and fruits, on hepatic cancer HepG2 cell proliferation, migration, invasion, and apoptosis, as well as microRNA-21 (miR-21) expression. Cell viability was detected using cell counting kit-8 (CCK-8) assay. Cell proliferation was measured using 5-bromo-2′-deoxyuridine (BrdU) incorporation assay. Cell apoptosis was assessed using Guava Nexin assay. Cell migration and invasion were determined using two-chamber migration (invasion) assay. Cell transfection was used to change the expression of miR-21. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed to analyze the expressions of miR-21 and phosphatase and tensin homologue (PTEN). Expression of key proteins involved in proliferation, apoptosis, migration, invasion, and phosphatidylinositol 3-kinase/protein kinase 3/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway were evaluated using western blotting. Results showed that kaempferol significantly inhibited HepG2 cell proliferation, migration, and invasion, and induced cell apoptosis. Kaempferol remarkably reduce the expression of miR-21 in HepG2 cells. Overexpression of miR-21 obviously reversed the effects of kaempferol on HepG2 cell proliferation, migration, invasion, and apoptosis. Moreover, miR-21 negatively regulated the expression of PTEN in HepG2 cells. Kaempferol enhanced the expression of PTEN and inactivated PI3K/AKT/mTOR signaling pathway in HepG2 cells. In conclusion, kaempferol inhibited proliferation, migration, and invasion of HepG2 cells by down-regulating miR-21 and up-regulating PTEN, as well as inactivating PI3K/AKT/mTOR signaling pathway.

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Polyphyllin I Promoted Melanoma Cells Autophagy and Apoptosis via PI3K/Akt/mTOR Signaling Pathway

BioMed Research International ◽

10.1155/2020/5149417 ◽

2020 ◽

Vol 2020 ◽

pp. 1-9

Author(s):

Jianwen Long ◽

Xianming Pi

Keyword(s):

Cell Cycle ◽

Cell Proliferation ◽

Signaling Pathway ◽

Melanoma Cell ◽

Cell Apoptosis ◽

Signal Pathway ◽

Mtor Signaling ◽

Mtor Signaling Pathway ◽

A375 Cells

To investigate whether Polyphyllin I (PPI) might induce the autophagy and apoptosis of melanoma cells by regulating PI3K/Akt/mTOR signal pathway. Melanoma A375 cells were incubated with different concentrations of Polyphyllin I (0, 1.5, 3.0, and 6.0 mg/L) and PI3K/Akt/mTOR signaling pathway activator IGF-1(20 mg/L). CCK-8 assay was utilized to detect cell proliferation; Cell apoptosis and cell cycle were measured by flow cytometry; Western blot was used to examine the expressions of proteins. Immunofluorescence analysis was performed to evaluate autophagy of A375 cells; In addition, xenograft-bearing nude mice were applied to study the role of Polyphyllin I on melanoma development, melanoma cell proliferation, as well as melanoma cell apoptosis in vivo. The outcomes represented that Polyphyllin I promoted A375 cell apoptosis via upregulating Bax level and cleaved caspase-3 level and downregulating Bcl-2 level, inhibited the growth of A375 cells at the G0/G1 phase, and enhanced cell autophagy via regulating the levels of Beclin 1, LC3II, and p62. However, IGF-1 (an activator of PI3K/Akt/mTOR signal pathway) attenuated these changes that Polyphyllin I induced. Furthermore, the xenograft model experiment confirmed that Polyphyllin I treatment suppressed xenograft tumor growth, increased apoptotic index evaluated by the TUNEL method, and reduced the level of Ki67 in tumor tissues in vivo. In conclusion, Polyphyllin I treatment enhanced melanoma cell autophagy and apoptosis, as well as blocked melanoma cell cycle via suppressing PI3K/Akt/mTOR signal pathway. Meanwhile, Polyphyllin I treatment suppressed the development of melanoma in vivo. Therefore, Polyphyllin I possibly is a promising molecular targeted agent used in melanoma therapy.

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LncRNA TP73-AS1 Promotes Cell Proliferation and Inhibits Cell Apoptosis in Clear Cell Renal Cell Carcinoma Through Repressing KISS1 Expression and Inactivation of PI3K/Akt/mTOR Signaling Pathway

Cellular Physiology and Biochemistry ◽

10.1159/000491767 ◽

2018 ◽

Vol 48 (1) ◽

pp. 371-384 ◽

Cited By ~ 29

Author(s):

Guanghua Liu ◽

Xin Zhao ◽

Jingmin Zhou ◽

Xiangming Cheng ◽

Zixing Ye ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Proliferation ◽

Cell Carcinoma ◽

Signaling Pathway ◽

Cell Apoptosis ◽

Renal Cell ◽

Clear Cell ◽

Mtor Signaling ◽

Metastasis Suppressor ◽

Mtor Signaling Pathway

Background/Aims: Emerging evidence suggests that long non-coding RNAs (lncRNAs) play a vital regulatory role in the pathogenesis and progression of renal cell carcinoma (RCC). We aim to determine lncRNA profiles in clear cell RCC (ccRCC) and investigate key lncRNAs involved in ccRCC tumorigenesis and progression. Methods: RNA sequencing technique and qPCR were used to determine the candidate lncRNAs in ccRCC tissues. The correlations between lncRNA P73 antisense RNA 1T (TP73-AS1) levels and survival outcomes were analyzed to elucidate its clinical significance. The underlying mechanisms of TP73-AS1 in ccRCC were analyzed through in vitro functional assays. Results: We found TP73-AS1 was upregulated in 40 ccRCC tissues compared with adjacent normal renal tissues and increased TP73-AS1 was correlated to aggressive clinicopathologic features and unfavorable prognosis. Knockdown of TP73-AS1 suppressed cell proliferation, invasion and induced cell apoptosis. We also identified KISS-1 metastasis-suppressor (KISS1) was significantly upregulated in TP73-AS1 knockdown cells. Further, we revealed that TP73-AS1 suppressed KISS1 expression through the interaction with Enhancer of zeste homolog 2 (EZH2) and the specific binding to KISS1 gene promoter region. Knockdown of KISS1 partly reversed TP73-AS1 knockdown-induced inhibition of cell proliferation and promotion of apoptosis. We further determined that TP73-AS1 knockdown activated PI3K/Akt/mTOR signaling pathway, while overexpression of TP73-AS1 induced inhibition of PI3K/Akt/mTOR pathway and these effects could be partly abolished by overexpression of KISS1. Conclusion: In conclusion, we identified that TP73-AS1 as an oncogenic lncRNA in the development of ccRCC and a potential target for human renal carcinoma treatment.

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Cordycepin augments the chemosensitivity of osteosarcoma to cisplatin by activating AMPK and suppressing the AKT signaling pathway

Cancer Cell International ◽

10.1186/s12935-021-02411-y ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Hong-Bo Li ◽

Jun-Kai Chen ◽

Ze-Xin Su ◽

Qing-Lin Jin ◽

Li-Wen Deng ◽

...

Keyword(s):

Cell Proliferation ◽

Signaling Pathway ◽

Cell Apoptosis ◽

Mtor Signaling ◽

Osteosarcoma Cell ◽

Mtor Signaling Pathway ◽

Osteosarcoma Cells ◽

Related Proteins

Abstract Background Osteosarcoma is the most common primary bone tumor in children and adolescents. However, some patients with osteosarcoma develop resistance to chemotherapy, leading to a poor clinical prognosis. Hence, effective therapeutic agents that can improve the response to chemotherapy drugs to improve the prognosis of patients with osteosarcoma are urgently needed. Cordycepin has recently emerged as a promising antitumor drug candidate. This study aims to explore the effect of cordycepin in suppressing osteosarcoma in vivo and in vitro and the synergistic effect of cordycepin combined with cisplatin and to demonstrate the underlying molecular mechanism. Methods CCK-8 assay was performed to investigate the inhibition effect of cordycepin combined with cisplatin in osteosarcoma cell lines. The colony formation and invasion abilities were measured by colony formation assay and Transwell assay. Osteosarcoma cells apoptosis was detected by flow cytometry. Western blot analysis were used to detect the expression of cell apoptosis-related proteins and AMPK and AKT/mTOR signaling pathway-related proteins. Finally, we performed the in vivo animal model to further explore whether cordycepin and cisplatin exert synergistic antitumor effects. Results Notably, we found that treatment with cordycepin inhibited cell proliferation, invasion, and induced apoptosis in osteosarcoma cells in vitro and in vivo. Moreover, the combination of cordycepin and cisplatin led to marked inhibition of osteosarcoma cell proliferation and invasion and promoted osteosarcoma cell apoptosis in vitro and in vivo. Mechanistically, we demonstrated that cordycepin enhanced the sensitivity of osteosarcoma cells to cisplatin by activating AMPK and inhibiting the AKT/mTOR signaling pathway. Conclusions In brief, this study provides comprehensive evidence that cordycepin inhibits osteosarcoma cell growth and invasion and induces osteosarcoma cell apoptosis by activating AMPK and inhibiting the AKT/mTOR signaling pathway and enhances the sensitivity of osteosarcoma cells to cisplatin, suggesting that cordycepin is a promising treatment for osteosarcoma.

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STYX/FBXW7 axis participates in the development of endometrial cancer cell via Notch–mTOR signaling pathway

Bioscience Reports ◽

10.1042/bsr20200057 ◽

2020 ◽

Vol 40 (4) ◽

Author(s):

Liheng Liu ◽

Haili Jiang ◽

Xiaoxin Wang ◽

Xin Wang ◽

Liying Zou

Keyword(s):

Cell Proliferation ◽

Endometrial Cancer ◽

Signaling Pathway ◽

Cell Apoptosis ◽

Notch Pathway ◽

Mtor Signaling ◽

Expression Level ◽

Mtor Signaling Pathway ◽

Ec Cells ◽

The Impact

Abstract Endometrial cancer (EC) is the most common gynecologic malignancy in world. It has been reported that the mutation rate of FBXW7 is frequent in EC, but the specific functions of FBXW7 remain unknown in EC. In the present study, we revealed the role and mechanism of FBXW7 in EC cells. Compared with adjacent nontumor tissues, the FBXW7 expression level was lower in EC tissues. However, the level of STYX was in contrast with the expression of FBXW7 in EC tissues. And STYX interacted with FBXW7 and then down-regulated its expression level in EC. Over-expression of FBXW7 inhibited cell proliferation and facilitated apoptosis in EC cells, whereas silencing FBXW7 acted an opposite effect on EC cells. And the process of FBXW7 participated the proliferation and apoptosis in EC was regulated by STYX. FBXW7 suppressed the expression of Notch pathway related protein, and further inhibited the phosphorylation of mTOR. In addition, we also found that mTOR activitor (MHY1485) and Notch activator (Jagged-1) reversed the effect of over-expressing FBXW7 on cell proliferation and cell apoptosis. And Notch inhibitor (DAPT) counteracted the impact of over-expressing STYX on cell proliferation and cell apoptosis. Collectively, the present study verified that STYX inhibited the expression level of FBXW7 in EC, and then promoted cell proliferation but suppressed apoptosis through Notch–mTOR signaling pathway, which promoted carcinogenesis and progression of EC.

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Upregulation of Long Noncoding RNA_GAS5 Suppresses Cell Proliferation and Metastasis in Laryngeal Cancer via Regulating PI3K/AKT/mTOR Signaling Pathway

Technology in Cancer Research & Treatment ◽

10.1177/1533033821990074 ◽

2021 ◽

Vol 20 ◽

pp. 153303382199007

Author(s):

Wenlin Liu ◽

Jiandong Zhan ◽

Rong Zhong ◽

Rui Li ◽

Xiaoli Sheng ◽

...

Keyword(s):

Cell Proliferation ◽

Signaling Pathway ◽

Laryngeal Cancer ◽

Mtor Signaling ◽

Mtor Signaling Pathway ◽

Proliferation And Metastasis ◽

Cancer Tissues ◽

Lncrna Gas5

Background: Laryngeal cancer is one of the most common malignant tumors among head and neck cancers. Accumulating studies have indicated that long noncoding RNAs (lncRNAs) play an important role in laryngeal cancer occurrence and progression, however, the functional roles and relative regulatory mechanisms of lncRNA growth arrest-specific transcript 5 (GAS5) in laryngeal cancer progression remain unclear. Methods: The expression of lncRNA GAS5 in both laryngeal cancer tissues and cell lines was evaluated using quantitative reverse transcription-polymerase chain reaction (RT-qPCR) assay. The relationships between lncRNA GAS5 expression and clinical parameters were also analyzed. To determine the biological function of lncRNA GAS5, a lncRNA GAS5-specific plasmid was first transfected into laryngeal cancer cells using lentiviral technology. Cell counting kit-8 assay, flow cytometry, and Transwell assays were used to detect in vitro cell proliferation, apoptosis, cycle distribution, and metastasis abilities, respectively. Furthermore, in vivo cell growth experiments were also performed using nude mice. Additionally, western blotting was performed to identify the underlying regulatory mechanism. Results: In the current study, lncRNA GAS5 was downregulated in laryngeal cancer tissues and its low expression was closely associated with poor tumor differentiation, advanced TNM stage, lymph node metastasis, and shorter overall survival time. In addition, lncRNA GAS5 upregulation significantly inhibited laryngeal cancer cell proliferation both in vitro and in vivo. Moreover, in response to lncRNA GAS5 overexpression, more laryngeal cancer cells were arrested at the G2/M stage, accompanied by increased cell apoptosis rates and suppressed migration and invasion capacities. Mechanistically, our data showed that the overexpression of lncRNA GAS5 significantly regulated the PI3K/AKT/mTOR signaling pathway. Conclusion: LncRNA GAS5 might act as a suppressor gene during laryngeal cancer development, as it suppressed cell proliferation and metastasis by regulating the PI3K/AKT/mTOR signaling pathway; thus, lncRNA GAS5 is a promising therapeutic biomarker for the treatment of laryngeal cancer.

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MicroRNA miR-106a-5p targets forkhead box transcription factor FOXC1 to suppress the cell proliferation, migration, and invasion of ectopic endometrial stromal cells via the PI3K/Akt/mTOR signaling pathway

Bioengineered ◽

10.1080/21655979.2021.1933679 ◽

2021 ◽

Vol 12 (1) ◽

pp. 2203-2213

Author(s):

Xinyue Zhou ◽

Zhenyu Chen ◽

Lipeng Pei ◽

Jingli Sun

Keyword(s):

Cell Proliferation ◽

Transcription Factor ◽

Signaling Pathway ◽

Stromal Cells ◽

Mtor Signaling ◽

Migration And Invasion ◽

Mtor Signaling Pathway ◽

Endometrial Stromal Cells ◽

Forkhead Box

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Silencing long non-coding RNA ROR improves sensitivity of non-small-cell lung cancer to cisplatin resistance by inhibiting PI3K/Akt/mTOR signaling pathway

Tumor Biology ◽

10.1177/1010428317697568 ◽

2017 ◽

Vol 39 (5) ◽

pp. 101042831769756 ◽

Cited By ~ 31

Author(s):

Hui Shi ◽

Jin Pu ◽

Xiao-Li Zhou ◽

Yun-Ye Ning ◽

Chong Bai

Keyword(s):

Cell Proliferation ◽

Signaling Pathway ◽

Negative Control ◽

Mtor Signaling ◽

Mtor Signaling Pathway ◽

Control Groups ◽

Over Expression ◽

Non Coding Rna ◽

Protein Expressions ◽

Long Non Coding Rna

This study aimed to investigate the effects of long non-coding RNA ROR (regulator of reprogramming) on cisplatin (DDP) resistance in patients with non-small-cell lung cancer by regulating PI3K/Akt/mTOR signaling pathway. Human cisplatin-resistant A549/DDP cell lines were selected and divided into control group, negative control group, si-ROR group, ROR over-expression group, Wortmannin group, and ROR over-expression + Wortmannin group. MTT assay was used to determine the optimum inhibitory concentration of DDP. Quantitative real-time polymerase chain reaction and western blotting were applied to detect expressions of long non-coding RNA ROR, PI3K, Akt, and mTOR. Colony-forming assay, scratch test, Transwell assay, and flow cytometry were conducted to detect cell proliferation, migration, invasion, and apoptosis, respectively. Tumor-formation assay was performed to detect the growth of transplanted tumors. Long non-coding RNA ROR expression was high in human A549/DDP cell lines. Compared with the control and negative control groups, the mRNA and protein expressions of PI3K, Akt, mTOR, and bcl-2 decreased, whereas the mRNA and protein expression of bax and the sensitivity of cells to DDP significantly increased. Cell proliferation, migration, and invasion abilities decreased in the si-ROR and Wortmannin groups. In comparison with control and negative control groups, the mRNA and protein expressions of PI3K, Akt, mTOR, and bcl-2 increased, whereas the mRNA and protein expressions of bax decreased, the sensitivity of cells to DDP significantly increased, and cell proliferation, migration, and invasion abilities decreased in the ROR over-expression group. For nude mice in tumor-formation assay, compared with control and negative control groups, the tumor weight was found to be lighter (1.03 ± 0.15) g, the protein expressions of PI3K, Akt, mTOR, and bcl-2 decreased, and the protein expression of bax increased in the si-ROR group. Long non-coding RNA ROR may affect the sensitivity of lung adenocarcinoma cells to DDP by targeting PI3K/Akt/mTOR signaling pathway.

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