scholarly journals Kaempferol inhibits proliferation, migration, and invasion of liver cancer HepG2 cells by down-regulation of microRNA-21

2018 ◽  
Vol 32 ◽  
pp. 205873841881434 ◽  
Author(s):  
Genglong Zhu ◽  
Xialei Liu ◽  
Haijing Li ◽  
Yang Yan ◽  
Xiaopeng Hong ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Liver Cancer ◽  
Signaling Pathway ◽  
Hepg2 Cell ◽  
Cell Apoptosis ◽  
Hepg2 Cells ◽  
Mtor Signaling ◽  
Brdu Incorporation ◽  
Migration And Invasion ◽  
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.

scholarly journals MiR-496 Inhibits the Proliferation Through Targeting LYN and AKT/mTOR Signaling Pathway in Gastric Cancer

2020 ◽  
Author(s):  
Rui Su ◽  
Enhong Zhao ◽  
Jun Zhang
Keyword(s):  
Gastric Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Mtor Signaling ◽  
Migration And Invasion ◽  
Human Gastric Cancer ◽  
Mtor Signaling Pathway ◽  
Gastric Cancer Cells ◽  
Ags Cells

Abstract MiRNA operates as a tumor suppressor or carcinogen to regulate cell proliferation, metastasis, invasion, differentiation, apoptosis and metabolic process. In the present research, we investigated the effect and mechanism of miR496 in human gastric cancer cells. Cell proliferation was measured by CCK8 and clonogenic assay. Transwell test was performed to detect cell migration and invasion. Flow cytometry analysis was used to evaluate cell apoptosis. Bioinformatics software targetscan was used for the screening of miR-496’s target gene. MiR-496 was down regulated in three gastric cancer cell lines, SGC-790, AGS and MKN45 compared with normal gastric epithelial cell line GES-1. MiR-496 mimics inhibited the proliferation of AGS cells after the transfection for 48 h and 72 h. The migration and invasion of AGS cells were also inhibited by the transfection of miR-496 mimics. In addition, miR-496 mimics induced the apoptosis through up regulating the levels of Bax and Active Caspase3 and down regulating the levels of Bcl-2 and Total Caspase3. Bioinformatics analysis showed that there was a binding site between miR-496 and LYN kinase (LYN). MiR-496 mimics could inhibit the expression of LYN in AGS cells. The overexpression of LYN blocked the inhibition of tumor cell growth, as well as the inhibition of AKT/mTOR signaling pathway induced by miR-496 in gastric cancer cells. In conclusion, miR-496 inhibited the proliferation through the AKT/mTOR signaling pathway via targeting LYN in gastric cancer cells. Our research provides a new potential target for clinical diagnosis and targeted treatment of gastric cancer.

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

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.

scholarly journals 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

2018 ◽  
Vol 48 (1) ◽  
pp. 371-384 ◽  
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.

scholarly journals Knockdown of DDX46 inhibits trophoblast cell proliferation and migration through the PI3K/Akt/mTOR signaling pathway in preeclampsia

2020 ◽  
Vol 15 (1) ◽  
pp. 400-408
Author(s):  
Xin You ◽  
Hongyan Cui ◽  
Ning Yu ◽  
Qiuli Li
Keyword(s):  
Cell Proliferation ◽  
Signaling Pathway ◽  
Trophoblast Cell ◽  
Mtor Signaling ◽  
Migration And Invasion ◽  
Mrna Levels ◽  
Loss Of Function ◽  
Mtor Signaling Pathway ◽  
Trophoblast Cells ◽  
And Migration

AbstractPreeclampsia (PE) is a serious disease during pregnancy associated with the dysfunction of trophoblast cell invasion. DDX46 is a kind of RNA helicase that has been found to regulate cancer cell metastasis. However, the role of DDX46 in PE remains unclear. Our results showed that the mRNA levels of DDX46 in placental tissues of pregnant women with PE were markedly lower than those in normal pregnancies. Loss-of-function assays showed that knockdown of DDX46 significantly suppressed cell proliferation of trophoblast cells. Besides, DDX46 knockdown decreased trophoblast cell migration and invasion capacity. In contrast, the overexpression of DDX46 promoted the migration and invasion of trophoblast cells. Furthermore, knockdown of DDX46 caused significant decrease in the levels of p-PI3K, p-Akt, and p-mTOR in HTR-8/SVneo cells. In addition, treatment with IGF-1 reversed the inhibitory effects of DDX46 knockdown on proliferation, migration, and invasion of HTR-8/SVneo cells. In conclusion, these data suggest that DDX46 might be involved in the progression of PE, which might be attributed to the regulation of PI3K/Akt/mTOR signaling pathway. Thus, DDX46 might serve as a therapeutic target for the treatment of PE.

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