scholarly journals The synergistic effects of Apatinib combined with cytotoxic chemotherapeutic agents on gastric cancer cells and in a fluorescence imaging gastric cancer xenograft model

2018 ◽  
Vol Volume 11 ◽  
pp. 3047-3057 ◽  
Author(s):  
Jiuhuan Feng ◽  
Shukui Qin
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Fluorescence Imaging ◽  
Synergistic Effects ◽  
Xenograft Model ◽  
Chemotherapeutic Agents ◽  
Gastric Cancer Cells ◽  
Gastric Cancer Xenograft

scholarly journals Cre-loxP-mediated bax gene activation reduces growth rate and increases sensitivity to chemotherapeutic agents in human gastric cancer cells

2000 ◽  
Vol 7 (6) ◽  
pp. 885-892 ◽  
Author(s):  
Koga Komatsu ◽  
Susumu Suzuki ◽  
Tooru Shimosegawa ◽  
Jun-ichi Miyazaki ◽  
Takayoshi Toyota
Keyword(s):  
Gastric Cancer ◽  
Growth Rate ◽  
Cancer Cells ◽  
Gene Activation ◽  
Chemotherapeutic Agents ◽  
Human Gastric Cancer ◽  
Gastric Cancer Cells ◽  
Bax Gene

scholarly journals Combination of Sodium Selenite and Doxorubicin Prodrug Ac-Phe-Lys-PABC-ADM Affects Gastric Cancer Cell Apoptosis in Xenografted Mice

2019 ◽  
Vol 2019 ◽  
pp. 1-8
Author(s):  
Bo Wu ◽  
Jian Ge ◽  
Zixiong Zhang ◽  
Chuying Huang ◽  
Xiaodan Li ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Sodium Selenite ◽  
Combined Treatment ◽  
Xenograft Model ◽  
Tumor Xenograft ◽  
Mitochondrial Apoptosis ◽  
Gastric Cancer Cells ◽  
Apoptosis Pathway

The incidence of gastric cancer is extremely high in China, prompting the development of effective therapeutic strategies. Sodium selenite (SS) affects the proliferation and redifferentiation of gastric cancer cells and the Adriamycin prodrug Ac-Phe-Lys-PABC-ADM (PADM) reduces toxicity in gastric cancer treatment. However, the mechanisms involved therein remain unclear. In this study, nude mice were transplanted with SGC-7901 gastric cancer cells to construct a tumor xenograft model. After administration of SS and PADM, tumor weight and size were reduced. In addition, the levels of alanine aminotransferase, aspartate transaminase, creatinine, and lactate dehydrogenase were decreased, indicating improved hepatic and renal function and inhibited cancer cell metabolism. Furthermore, combined treatment of SS and PADM downregulated the expression of cell cycle-related proteins (cyclin-dependent kinase 4, Ki67, cyclin E, and cyclin D1), elevated that of proapoptosis proteins (Bax, cleaved caspase-3, cleaved caspase-9, and P53), and upregulated that of mitochondrial apoptosis-associated proteins (apoptotic protease activating factor 1 and second mitochondria-derived activator of caspases). In conclusion, combined treatment of SS and PADM effectively promoted apoptosis in gastric cancer xenografts via the mitochondrial apoptosis pathway.

scholarly journals Exosomal Micro RNA-107 Reverses Chemotherapeutic Drug Resistance of Gastric Cancer Cells Through HMGA2/mTOR/P-gp Pathway

2021 ◽  
Author(s):  
Lu Jiang ◽  
Yan Zhang ◽  
Linghui Guo ◽  
Chaoyang Liu ◽  
Weihong Ren
Keyword(s):  
Gastric Cancer ◽  
Drug Resistance ◽  
Cancer Cells ◽  
Chemotherapeutic Agents ◽  
Luciferase Reporter Assay ◽  
Luciferase Reporter ◽  
Reporter Assay ◽  
Gastric Cancer Cells ◽  
Chemotherapy Drug ◽  
Chemotherapy Drugs

Abstract Background: RNA cargo in exosomes，especially microRNAs (miRNAs), play an important role in the chemotherapy drug resistance of human cancers. However, the role and mechanism of exosomal miR-107 on multidrug resistance of gastric cancer cells was still not clear. In this study, we sought to explore whether exosomal miR-107 could reverse theresistance of gastric cancer cells to the chemotherapy drugs. Methods: We extracted exosomes from sensitive (SGC-7901, MGC-803) and resistant (SGC-7901/5-FU) gastric cancer cells by ultracentrifugation and the isolated exosomes were identified using transmission electron microscopy (TEM) and dynamic light scattering analysis (DLS). The expression of miR-107 and high mobility group A2 (HMGA2) were detected by real-time quantitative PCR (RT-qPCR). MTT assay was used to investigate the effect of exosomes on gastric cancer cells growth in vitro. The uptake of exosomes by recipient cells were observed using a fluorescence microscope. The predicted target relationship between miR-107 and HMGA2 was verified by gauss-luciferase reporter assay. The expression of HMGA2, p-mTOR/mTOR, P-gp and other exosomal indicated marker proteins were detected by western blot. Results: Our results indicated that the isolated exosomes were demostrated typically cup-like lipid bilayer membrans structure. SGC-7901/5-FU cells were cross-resistant to chemotherapy drug cisplatin (DDP), and the sensitive cells-secreted exosomes drastically reversed the resistance of the resistant gastric cells to the chemotherapeutic drugs,which was verificated by exosomal inhibitor GW4896. Mechanistically, the reversal effect were mainly mediated by exosome-secreted miR-107 through downregulating the expression of targert molecular HMGA2, and inhibiting HMGA2/mTOR/P-gp pathway, which were proofed by luciferase reporter assay and rescue assay. Conclusions: These findings demonstrated that exosome-transmitted miR-107 significantly enhanced the sensitivity of resistant gastric cancer cells to chemotherapeutic agents by mediating the HMGA2/mTOR/P-gp axis and appling exosomal miR-107 may be a novel target in gastric cancers treatment.

scholarly journals Ursolic Acid Inhibits Epithelial-Mesenchymal Transition through the Axl/NF-κB Pathway in Gastric Cancer Cells

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Jinxia Li ◽  
Chunyan Dai ◽  
Li Shen
Keyword(s):  
Gastric Cancer ◽  
Cell Proliferation ◽  
Cell Migration ◽  
Western Blot ◽  
Cancer Cells ◽  
Ursolic Acid ◽  
Epithelial Mesenchymal Transition ◽  
Xenograft Model ◽  
Gastric Cancer Cells ◽  
Mesenchymal Transition

Background. Ursolic acid (UA) is an antitumor component derived from Chinese herbal medicine; this study is to observe the effects of UA on epithelial-mesenchymal transition (EMT) in gastric cancer. Methods. (1) In vitro experiments: 25μmol/L and 50μmol/L UA were applied to BGC-823, AGS, MGC-803, and HGC-27 cells; MTT staining, Transwell assay, and flow cytometry were used to assess cell proliferation, cell migration, and apoptosis, respectively. Western blot was performed to detect the expressions of N-Cadherin, Vimentin, Snail, Twist, Axl, p-Axl, IKK, p-IKK, NF-κB, and p-NF-κB. (2) In vivo experiments: Ten BALB/c-nu mice were used to establish gastric cancer xenograft model. Five were orally given UA for 4 weeks and five were given normal saline. Expressions of N-Cadherin and Snail were examined by immunohistochemical assay; expressions of N-Cadherin, Snail, Twist, Axl, p-Axl, IKK, and p-IKK were detected by Western blot. Results. (1) UA inhibited cell proliferation in BGC-823 and HGC-27 cells in dose-dependent manners. (2) UA inhibited cell migration in BGC-823, AGS, and MGC-803 cells while inducing apoptosis in BGC-823 cells. (3) UA significantly decreased the expressions of N-Cadherin, Vimentin, Snail, Twist p-Axl, p-IKKα/β, and p-NF-κB in BGC-823 and MGC-803 cells. (4) UA distinctly decreased the expressions of N-Cadherin, Snail, p-Axl, and p-IKKα/β in gastric cancer xenograft model rats. Conclusion. UA can effectively inhibit the proliferation and migration and induce apoptosis of gastric cancer cells. The antitumor effect of UA is conducted by EMT inhibition, which may be associated with the regulation of Axl/NF-κB signaling pathway.

Polyamine synthesis enzyme AMD1 is closely associated with tumorigenesis and prognosis of human gastric cancers

2019 ◽  
Vol 41 (2) ◽  
pp. 214-222 ◽  
Author(s):  
Lijiao Xu ◽  
Xue You ◽  
Qianqian Cao ◽  
Meiqin Huang ◽  
Lian-Lian Hong ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Xenograft Model ◽  
Expression Level ◽  
Tumor Xenograft ◽  
Blood Vessel Invasion ◽  
Human Gastric Cancer ◽  
Gastric Cancer Cells ◽  
Gastric Cancers ◽  
Normal Tissues

Abstract Adenosylmethionine decarboxylase 1 (AMD1) is a key enzyme involved in biosynthesis of polyamines including spermidine and spermine. The potential function of AMD1 in human gastric cancers is unknown. We analyzed AMD1 expression level in 319 human gastric cancer samples together with the adjacent normal tissues. The protein expression level of AMD1 was significantly increased in human gastric cancer samples compared with their corresponding para-cancerous histological normal tissues (P < 0.0001). The expression level of AMD1 was positively associated with Helicobactor pylori 16sRNA (P < 0.0001), tumor size (P < 0.0001), tumor differentiation (P < 0.05), tumor venous invasion (P < 0.0001), tumor lymphatic invasion (P < 0.0001), blood vessel invasion (P < 0.0001), and tumor lymph node metastasis (TNM) stage (P < 0.0001). Patients with high expression of AMD1 had a much shorter overall survival than those with normal/low expression of AMD1. Knockdown of AMD1 in human gastric cancer cells suppressed cell proliferation, colony formation and cell migration. In a tumor xenograft model, knockdown of AMD1 suppressed the tumor growth in vivo. Inhibition of AMD1 by an inhibitor SAM486A in human gastric cancer cells arrested cell cycle progression during G1-to-S transition. Collectively, our studies at the cellular, animal and human levels indicate that AMD1 has a tumorigenic effect on human gastric cancers and affect the prognosis of the patients.

scholarly journals Efficacy of Metformin and Chemotherapeutic Agents on the Inhibition of Colony Formation and Shh/Gli1 Pathway: Metformin/Docetaxel Versus Metformin/5-Fluorouracil

Drug Research ◽  
2020 ◽  
Vol 71 (01) ◽  
pp. 17-25
Author(s):  
Maryam Fatehi-Agdam ◽  
Mohammad Amin Vatankhah ◽  
Reza Panahizadeh ◽  
Farhad Jeddi ◽  
Nowruz Najafzadeh
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Cell Line ◽  
Gastric Cancer Cell ◽  
Gastric Cancer Cell Line ◽  
Cancer Cell Line ◽  
Chemotherapeutic Agents ◽  
Gastric Cancer Cells ◽  
Anticancer Effects ◽  
Chemotherapy Agents

Abstract Background Gastric cancer is a common gastrointestinal cancer characterized by poor prognosis and chemoresistance. Docetaxel and 5-fluorouracil (5-FU) are frequently used for the treatment of gastric cancer. Despite their potent anti-cancer effects, chemoresistance occurs in metastatic gastric cancer. Metformin, a popular anti-diabetic drug, has been proven to have potent anticancer effects on gastrointestinal cancers. Here, we aim to improve this chemotherapy agents’ efficacy by pretreatment with metformin. Methods The AGS gastric cancer cell line were pretreated with three different sub-toxic concentration of metformin and then treated with various concentrations of 5-FU and docetaxel.The anticancer effects of the combination of metformin with the chemotherapy agents were determined using clonogenic assay and DAPi staining. We used real-time PCR to evaluate Gli1, Gli2, and TWIST1 mRNA expression levels in the gastric cancer cells. Also, the expression of the Shh protein was assessed using immunocytochemistry. Results Here, we found that metformin sensitized the gastric cancer cells to chemotherapy. The combination treatments were more effective in reducing the number of cancer colonies compared to 5-FU or docetaxel alone. The combination of metformin with 5-FU or docetaxel significantly reduced the number of cells expressing the Shh protein compared to the 5-FU alone or docetaxel alone. Interestingly, we found that the combination of metformin with docetaxel significantly down-regulated the mRNA levels of Gli1, Gli2, and TWIST1 in the AGS gastric cancer cell line compared to docetaxel alone. Conclusion Overall, our data strongly support an important role for metformin as an enhancer of the efficacy of chemotherapeutic agents against gastric cancer.

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