Celastrol Inhibits the Proliferation and Decreases Drug Resistance of Cisplatin-Resistant Gastric Cancer SGC7901/DDP Cells

Background: This study aimed to determine the effect and mechanism of Celastrol inhibiting the proliferation and decreases drug resistance of cisplatin-resistant gastric cancer cells. Objective: To explore the effect and mechanism of Celastrol on proliferation and drug resistance of human gastric cancer cisplatin-resistant cells SGC7901/DDP. Methods: The thiazole blue (MTT) method was used to detect the sensitivity of human gastric cancer cisplatin-resistant cells SGC7901/DPP to cisplatin and Celastrol to determine the Drug resistance index (DRI). According to the half inhibitory concentration (IC50) value, the action concentration of the following experimental drugs was set to reduce the cytotoxicity; Annexin V-FITC/PI double staining method was used to detect the apoptosis of SGC7901/DDP cells induced by Celastrol; Western Blot was used to examine the expression levels of P-glycoprotein (P-gp), Multidrug Resistance Associated Protein 1 (MRP1), Breast Cancer Resistance Associated Protein (Breast Cancer Resistance)-relative protein (BCRP), and mechanistic Target of Rapamycin (mTOR) pathway related proteins; Real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) was used to detect the mRNA expression levels of P-gp, MRP1, and BCRP. Results: (1) Compared with the control group (We set the untreated group as the control group), the proliferation of the SGC7901/DPP cells was significantly inhibited after treating with 0.1-6.4μmol/L Celastrol in a time- and concentration-dependent manner (P<0.05). The Drug resistance index DRI of the SGC7901/DPP cells to DDP was 5.64. (2) Compared with the control group, Celastrol could significantly inhibit the proliferation and induce the apoptosis of the SGC7901/DPP cells (P<0.05). (3) The mRNA and protein expression levels of P-gp, MRP1, and BCRP in the SGC7901/DPP cells were significantly higher than those in the SGC7901 cells. However, after treating with Celastrol, the expression levels of P-gp, MRP1, and BCRP in the SGC7901/DPP cells were significantly reduced (P<0.05). (4) Compared with the control group, the Celastrol treatment also reduced the expression of the mTOR signaling pathway related proteins, suggesting that the mTOR signaling pathway may be involved in the process of Celastrol inhibiting the proliferation of the SGC7901/DDP cells and reducing their drug resistance. (5) Significantly, the combination of Celastrol and DDP reduced the expression of P-gp, MRP1, and BCRP in the SGC7901/DPP cells. Conclusion: Celastrol can inhibit the proliferation of the SGC7901/DDP cells, induce their apoptosis, and reduce the expression of drug resistance genes, probably by inhibiting the expression of the proteins related to the mTOR signaling pathway.

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

10.21203/rs.3.rs-61573/v1 ◽

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.

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Oncogenic NanogP8 expression regulates cell proliferation and migration through the Akt/mTOR signaling pathway in human gastric cancer – SGC-7901cell line

OncoTargets and Therapy ◽

10.2147/ott.s97861 ◽

2016 ◽

Vol Volume 9 ◽

pp. 4859-4866 ◽

Cited By ~ 5

Author(s):

Zheng Jiang ◽

Yao Liu ◽

Chuan Wang

Keyword(s):

Gastric Cancer ◽

Cell Proliferation ◽

Signaling Pathway ◽

Mtor Signaling ◽

Human Gastric Cancer ◽

Mtor Signaling Pathway ◽

Cell Proliferation And Migration ◽

And Migration ◽

Proliferation And Migration

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Celastrus Orbiculatus Extracts Inhibit the Metastasis through Attenuating PI3K/Akt/mTOR Signaling Pathway in Human Gastric Cancer

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520619666190731162722 ◽

2019 ◽

Vol 19 (14) ◽

pp. 1754-1761 ◽

Cited By ~ 2

Author(s):

Yayun Qian ◽

Yan Yan ◽

Hongmei Lu ◽

Tingting Zhou ◽

Mengying Lv ◽

...

Keyword(s):

Gastric Cancer ◽

Cancer Cells ◽

Signaling Pathway ◽

Mtor Signaling ◽

Human Gastric Cancer ◽

Celastrus Orbiculatus ◽

Mtor Signaling Pathway ◽

Gastric Cancer Cells ◽

Invasion And Migration ◽

And Migration

Background: Rapamycin receptor inhibitors have been applied in the clinic and achieved satisfactory therapeutic effect recently. The mechanisms did not clearly show how the Celastrus orbiculatus Extracts (COE) inhibited the expression of the mammalian Target of Rapamycin (mTOR) in human gastric cancer cells. The aim of this study was to investigate whether the COE inhibited the metastasis through the mTOR signaling pathway in human gastric cancer MGC-803 cells. Methods: The abnormal expression level of mTOR protein was detected by immunohistochemistry in human gastric cancer tissue. The MGC-803/mTOR- cells were constructed by knockdown of mTOR using lentivirus infection technique. The human gastric cancer MGC-803/mTOR- cells were treated with different concentrations (20, 40, 80 μg/ml) of COE for 24 hours. The ability of cell metastasis was analyzed by the cell invasion and migration assay. The expression levels of PI3K/Akt/mTOR signaling pathway were detected by Western Blotting. Results: COE inhibited the proliferation, invasion and migration of MGC-803/mTOR- cells in a concentrationdependent manner. The expression of E-cadherin protein increased, and the expression of N-cadherin and Vimentin decreased simultaneously in the MGC-803/mTOR- cells. 4EBP1, p-4EBP1, P70S6k, p-P70S6k, mTOR, p-mTOR, PI3K and Akt proteins in MGC-803/mTOR- cells were reduced in a dose-dependent manner. Conclusion: COE could not only inhibit cell growth, invasion and migration, but also inhibit the epithelialmesenchymal transition of gastric cancer cells. The molecular mechanism of COE inhibited the metastasis which may be related to the PI3K/Akt/mTOR signal pathway. This study provides ideas for the development of new anti-gastric cancer drugs.

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Methionine enkephalin (MENK) inhibits human gastric cancer through regulating tumor associated macrophages (TAMs) and PI3K/AKT/mTOR signaling pathway inside cancer cells

International Immunopharmacology ◽

10.1016/j.intimp.2018.10.023 ◽

2018 ◽

Vol 65 ◽

pp. 312-322 ◽

Cited By ~ 9

Author(s):

Xiaonan Wang ◽

Xue Jiao ◽

Yiming Meng ◽

Hao Chen ◽

Noreen Griffin ◽

...

Keyword(s):

Gastric Cancer ◽

Cancer Cells ◽

Signaling Pathway ◽

Mtor Signaling ◽

Human Gastric Cancer ◽

Mtor Signaling Pathway ◽

Tumor Associated Macrophages ◽

Methionine Enkephalin

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miR-496 inhibits proliferation via LYN and AKT pathway in gastric cancer

Open Medicine ◽

10.1515/med-2021-0313 ◽

2021 ◽

Vol 16 (1) ◽

pp. 1206-1214

Author(s):

Rui Su ◽

Enhong Zhao ◽

Jun Zhang

Keyword(s):

Gastric Cancer ◽

Cancer Cells ◽

Signaling Pathway ◽

Caspase 3 ◽

Mtor Signaling ◽

Migration And Invasion ◽

Human Gastric Cancer ◽

Mtor Signaling Pathway ◽

Gastric Cancer Cells ◽

Ags Cells

Abstract MicroRNAs (miRNAs) operate as 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 miR-496 in human gastric cancer cells. miR-496 was downregulated in two gastric cancer cell lines, 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 and 72 h. The migration and invasion of AGS cells were also inhibited by the transfection of miR-496 mimics. miR-496 mimics induced the apoptosis through upregulating the levels of Bax and Active Caspase 3 and downregulating the levels of Bcl-2 and Total Caspase 3. 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. LYN overexpression blocked the inhibition of tumor cell growth, as well as the inhibition of AKT/mTOR signaling pathway induced by miR-496. 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 for gastric cancer.

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The m6A methyltransferase METTL14 inhibits the proliferation, migration, and invasion of gastric cancer by regulating the PI3K/AKT/mTOR signaling pathway

Journal of Clinical Laboratory Analysis ◽

10.1002/jcla.23655 ◽

2020 ◽

Author(s):

Xin Liu ◽

Mingyang Xiao ◽

Liang Zhang ◽

Liuli Li ◽

Guolian Zhu ◽

...

Keyword(s):

Gastric Cancer ◽

Signaling Pathway ◽

Mtor Signaling ◽

Migration And Invasion ◽

Mtor Signaling Pathway

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The PI3K/Akt/mTOR signaling pathway in gastric cancer; from oncogenic variations to the possibilities for pharmacologic interventions

European Journal of Pharmacology ◽

10.1016/j.ejphar.2021.173983 ◽

2021 ◽

pp. 173983

Author(s):

Ayda Baghery Saghchy Khorasani ◽

Atieh Pourbagheri-Sigaroodi ◽

Ali Pirsalehi ◽

Ava Safaroghli-azar ◽

Mohammad Reza Zali ◽

...

Keyword(s):

Gastric Cancer ◽

Signaling Pathway ◽

Mtor Signaling ◽

Mtor Signaling Pathway

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Xihuang Pill inhibits the development of DMBA combined estrogen and progesterone induced breast precancerous lesions rats by PI3K/AKT/mTOR signaling pathway

10.21203/rs.3.rs-151758/v1 ◽

2021 ◽

Author(s):

Huanfang Fan ◽

Dehui Li ◽

Na Guo ◽

Chunxia Sun ◽

Jingfei Dong ◽

...

Keyword(s):

Protein Expression ◽

Signaling Pathway ◽

Breast Tissue ◽

Precancerous Lesions ◽

Precancerous Lesion ◽

Mtor Signaling ◽

Mtor Signaling Pathway ◽

Vegf Mrna ◽

Expression Levels ◽

Pten Mrna

Abstract Objective. To study the inhibitory effect of Xihuang Pill on the development of DMBA combined estrogen and progesterone induced breast precancerous lesions rats by PI3K/AKT/mTOR signaling pathway, and to explore the effect of Xihuang Pill in preventing and treating breast cancer. Method. Establishment of a rat model of breast precancerous lesion with DMBA combined estrogen and progesterone sequential induction for 10 weeks. Xihuang Pill was administered by gavage continuously for 4 weeks. Take rat breast tissue and stain with hematoxylin- eosin (HE). The pathomorphological changes were observed with light microscope; TUNEL staining to detect cell apoptosis in breast tissue; Western blot was used to detect the protein expression of P-PI3K, P-AKT (S473), P-AKT (T308), PTEN, P-Tuberin/TSC2, P-Tuberin (p-S939), p-mTOR, P-4E-BP1 in breast tissues. The qRT-PCR was used to detect the gene expression of PTEN mRNA and VEGF mRNA. Immunohistochemistry was used to detect the protein expression of P-S6, p-p70s6k and VEGF. Result. Compared with the disease model group, the low, middle and high dose Xihuang Pill groups could significantly reduce the degree of breast pathology, and the number of apoptosis of breast precancerous lesions cells increased with the increase of Xihuang Pill dose; The expression levels of P-PI3K, P-AKT (S473), P-AKT (T308), p-mTOR, P-4E-BP1, p-S6, p-p70S6K, VEGF protein and VEGF mRNA dropped with the increase of Xihuang Pill dose. The expression levels of PTEN, P-Tuberin/TSC2, P-Tuberin (p-S939) protein and PTEN mRNA elevated with the increase of Xihuang Pill dose. Conclusion. Xihuang Pill can promote the apoptosis of breast precancerous lesion cells and reduce the proliferation of vascular endothelial cells, and then inhibit the progression of breast precancerous lesions. Its mechanism probably associated with the regulation of PI3K/AKT/mTOR pathway related gene protein expression.

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