scholarly journals Narciclasine induces autophagy-mediated apoptosis in gastric cancer cells through the Akt/mTOR signaling pathway

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Yunfeng Yuan ◽  
Xue He ◽  
Xiang Li ◽  
Yan Liu ◽  
Yueliang Tang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Molecular Mechanisms ◽  
Biological Activities ◽  
Total Content ◽  
Autophagic Flux ◽  
Gastric Cancer Cells ◽  
Novel Therapy ◽  
Phosphorylation Level ◽  
Confocal Scanning

Abstract Background Gastric cancer is a common gastrointestinal cancer and currently has the third-highest mortality rate. Research shows that the natural compound narciclasine has a variety of biological activities. The present study aimed to investigate the effect of narciclasine on gastric cancer cells and its molecular mechanisms and determine whether this compound could be a novel therapy for gastric cancer. Methods MTT and clone assays were employed to detect the proliferation of gastric cancer cells. The cell apoptosis was detected by flow cytometry. The formation of autophagosomes and autophagosomal lysosomes was observed by transmission electron microscopy and laser confocal scanning microscopy. Western blotting was used to detect the expression of apoptosis, autophagy and Akt/mTOR pathway-related proteins. Results In this study, we found that narciclasine could inhibit the proliferation of gastric cancer cells and promote apoptosis in gastric cancer cells. Further experiments showed that narciclasine promoted the levels of autophagy proteins LC3-II, Atg-5 and Beclin-1, reduced the expression of the autophagy transporter p62, and increased autophagic flux. By using the autophagy inhibitors 3-MA and CQ, it was shown that narciclasine could induce autophagy-mediated apoptosis in gastric cancer cells. Finally, we found that narciclasine had no significant effects on the total content of Akt and mTOR in gastric cancer cells, and it involved autophagy in gastric cancer cells by reducing the phosphorylation level of p-Akt and p-mTOR. Conclusions Narciclasine can induce autophagy-dependent apoptosis in gastric cancer cells by inhibiting the phosphorylation level of Akt/mTOR and thus reduce the proliferation of gastric cancer cells.

Narciclasine Induces Autophagy-Mediated Gastric Cancer Cell Apoptosis Through The Akt/mTOR Signaling Pathway

2021 ◽  
Author(s):  
Yunfeng Yuan ◽  
Xue He ◽  
Xiang Li ◽  
Yan Liu ◽  
Yueliang Tang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Molecular Mechanisms ◽  
Gastric Cancer Cell ◽  
Biological Activities ◽  
Gastric Cancer Cells ◽  
Novel Therapy ◽  
Confocal Scanning ◽  
Gastric Cancer Cell Proliferation

Abstract Background: Gastric cancer is a common gastrointestinal cancer and currently has the third highest mortality rate. According to research, the natural compound narciclasine has a variety of biological activities. The aim of the present study was to investigate the effect of narciclasine on gastric cancer cells and its molecular mechanisms, to determine whether this compound could be a novel therapy to treat gastric cancer.Methods: MTT and clone assays were employed to detect the proliferation of gastric cancer cells. The apoptosis rate was detected by flow cytometry. The formation of autophagosomes and autophagosomal lysosomes was observed by transmission electron microscopy and laser confocal scanning microscopy. Western blotting was used to detect the expression of apoptosis, autophagy and Akt/mTOR pathway related proteins. Results: In this study, we found that narciclasine could inhibit the proliferation of the gastric cancer cells , and promote gastric cancer cells apoptosis. Further experiments showed that narciclasine promoted the expression of autophagy proteins LC3-II, Atg-5, Beclin-1, reduced the expression of the autophagy transporter p62, and increased autophagic fux. By using the autophagy inhibitors 3-MA and CQ, it was shown that narciclasine can induces autophagy-mediated apoptosis in gastric cancer cells. Finally, we found that narciclasine had no significant effects on the total Akt and mTOR contents of gastric cancer cells, it involved autophagy in gastric cancer cells by reduce the phosphorylation levels of p-Akt and p-mTOR. Conclusions: Taken together, narciclasine can induce autophagy-dependent apoptosis in gastric cancer cells by inhibiting the phosphorylation level of Akt/mTOR and thus reducing gastric cancer cell proliferation.

Effects and Mechanisms of Anlotinib and Dihydroartemisinin Combination Therapy in Ameliorating Malignant Biological Behavior of Gastric Cancer Cells

2020 ◽  
Vol 21 ◽  
Author(s):  
Qiong Luo ◽  
Suyun Zhang ◽  
Donghuan Zhang ◽  
Rui Feng ◽  
Nan Li ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Molecular Mechanisms ◽  
Chorioallantoic Membrane ◽  
Cell Counting ◽  
Biological Behavior ◽  
Gastric Cancer Cells ◽  
Invasion And Migration ◽  
Apoptosis Related Protein ◽  
And Migration

Background: Gastric cancer(GC) is currently one of the major malignancies that threatens human lives and health. Anlotinib is a novel small-molecule that inhibits angiogenesis to exert anti-tumor effects. However, the function in gastric cancer is incompletely understood. Objective: The aim of the present study was to investigate the anti-tumor effects and molecular mechanisms of anlotinib combined with dihydroartemisinin (DHA) in SGC7901 gastric cancer cells. Method: Different concentrations of anlotinib and DHA were used to treat SGC7901 gastric cancer cells, after which cell proliferation was measured. Drug interactions of anlotinib and DHA were analyzed by the Chou-Talalay method with CompuSyn software. proliferation, apoptosis, invasion, migration, and angiogenesis were measured using the cell counting kit-8 (CCK8) assay, flow cytometry, Transwell invasion assays, scratch assays, and chicken chorioallantoic membrane (CAM) assays. proliferation-associated protein (Ki67), apoptosis-related protein (Bcl-2), and vascular endothelial growth factor A (VEGF-A) were quantified by Western bloting. Results: The combination of 2.5 μmol/L of anlotinib and 5 of μmol/L DHA was highly synergistic in inhibiting cell growth, significantly increased the apoptosis rate and suppressed obviously the invasion and migration capability and angiogenesis of gastric cancer cells. In addition, the expression levels of Ki67, Bcl-2, and VEGF-A, as well as angiogenesis, were significantly decreased in the Combination of drugs compared with in control and either drug alone. Conclusion: The combination of anlotinib and DHA showed synergistic antitumor activity, suggesting their potential in treating patients with gastric cancer.

scholarly journals miR-125b Suppresses Proliferation and Invasion by Targeting MCL1 in Gastric Cancer

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Shihua Wu ◽  
Feng Liu ◽  
Liming Xie ◽  
Yaling Peng ◽  
Xiaoyuan Lv ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Therapeutic Potential ◽  
Clinical Stage ◽  
Gastric Cancer Cells ◽  
Gastric Cancer Progression

Understanding the molecular mechanisms underlying gastric cancer progression contributes to the development of novel targeted therapies. In this study, we found that the expression levels of miR-125b were strongly downregulated in gastric cancer and associated with clinical stage and the presence of lymph node metastases. Additionally, miR-125b could independently predict OS and DFS in gastric cancer. We further found that upregulation of miR-125b inhibited the proliferation and metastasis of gastric cancer cells in vitro and in vivo. miR-125b elicits these responses by directly targeting MCL1 (myeloid cell leukemia 1), which results in a marked reduction in MCL1 expression. Transfection of miR-125b sensitizes gastric cancer cells to 5-FU-induced apoptosis. By understanding the function and molecular mechanisms of miR-125b in gastric cancer, we may learn that miR-125b has the therapeutic potential to suppress gastric cancer progression and increase drug sensitivity to gastric cancer.

Effect of IL-11 stimulated by co-culture with CAF on metastasis of gastric cancer cells mediated by upregulation of MUC1.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 86-86
Author(s):  
Xiaoxun Wang ◽  
Xiaofang Che ◽  
Yunpeng Liu ◽  
Xiujuan Qu
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Molecular Mechanisms ◽  
Specific Inhibitor ◽  
Neutralizing Antibody ◽  
Tumor Stroma ◽  
Migration And Invasion ◽  
Gastric Cancer Cells ◽  
Stromal Fibroblasts ◽  
Complementary Approach

86 Background: Cancer-associated fibroblasts (CAFs), as the activated fibroblasts in tumor stroma, are important modifiers of tumor progression. However, the molecular mechanisms underlying the tumor-promoting properties of CAFs in gastric cancer remain unclear. Methods: We show that when CAFs co-cultured with gastric cancer cells, two kinds of cells produce significant amounts of interleukin-11 (IL-11). CAFs enhances the migration and invasion of gastric cancer cells through the secretion of IL-11 that activates JAK/STAT3 and MAPK/ERK pathways to upregulate MUC1 in gastric cancer cells, while deprivation of IL-11 using a neutralizing antibody or inhibition of JAK/STAT3 and MAPK/ERK pathway with specific inhibitor Stattic and PD-98059 markedly attenuates these phenotypes in gastric cancer cells induced by CAFs. Results: In this study, we find that CAFs in the tumor microenvironment promote the progression of gastric cancer through IL-11-JAK/STAT3 and MAPK/ERK signalings to upregulate MUC1. Conclusions: Taken together, these results suggest that CAFs promote the progression of gastric cancer and IL-11 targeted therapy could be a complementary approach against gastric cancer by exerting their action on stromal fibroblasts.

Chrysin Alters microRNAs Expression Levels in Gastric Cancer Cells: Possible Molecular Mechanism

Drug Research ◽  
2017 ◽  
Vol 67 (09) ◽  
pp. 509-514 ◽  
Author(s):  
Farideh Mohammadian ◽  
Younes Pilehvar-Soltanahmadi ◽  
Shahriar Alipour ◽  
Mehdi Dadashpour ◽  
Nosratollah Zarghami
Keyword(s):  
Gastric Cancer ◽  
Gastric Carcinoma ◽  
Cancer Cells ◽  
Molecular Mechanism ◽  
Molecular Mechanisms ◽  
Gastric Cancer Cells ◽  
Gastric Carcinoma Cell ◽  
Expression Levels ◽  
Mirnas Expression ◽  
Chemopreventive Activity

Abstract Background Gastric carcinoma still remains the second most common cause of cancer mortality in the world. Chrysin, as a flavone, has showed cancer chemopreventive activity. The cellular and molecular mechanisms of chrysin in cancer cells have not been fully understood. Objective In this study, we investigate expression levels of let-7a, miR-9, mir-18a, miR-21, miR-22, miR-34a, miR-126 and mir-221 to describe the anti-cancer effects of chrysin. Materials and Methods The cytotoxic effects of chrysin were assessed using MTT assay. The effect of chrysin on the microRNAs expression was determined by qRT-PCR. Results The MTT results for different concentrations of chrysin at different times on the Gastric carcinoma cells showed that IC50 for chrysin was 68.24 µM after 24 h of treatment. Expression analysis identified that miR-18, miR-21 and miR-221 were down regulated whereas let-7a, miR-9, miR-22, miR-34a and miR-126 were up regulated in Gastric carcinoma cell line (p<0.05). Conclusion Treatment with chrysin can alter the miRNAs expression and these findings might be an explanation for molecular mechanism of chrysin effect on gastric cancer.

scholarly journals UFM1 suppresses invasive activities of gastric cancer cells by attenuating the expression of PDK1 through PI3K/AKT signaling

2019 ◽  
Vol 38 (1) ◽  
Author(s):  
Jian-Xian Lin ◽  
Xin-Sheng Xie ◽  
Xiong-Feng Weng ◽  
Sheng-Liang Qiu ◽  
Changhwan Yoon ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Molecular Mechanisms ◽  
Akt Signaling ◽  
Invasion And Metastasis ◽  
Gastric Cancer Cells ◽  
Invasion And Migration ◽  
And Migration ◽  
Gastric Cancer Patients

Abstract Background UFM1 has been found to be involved in the regulation of tumor development. This study aims to clarify the role and potential molecular mechanisms of UFM1 in the invasion and metastasis of gastric cancer. Methods Expression of UFM1 in gastric tumor and paired adjacent noncancerous tissues from 437 patients was analyzed by Western blotting, immunohistochemistry, and realtime PCR. Its correlation with the clinicopathological characteristics and prognosis of gastric cancer patients was analyzed. The effects of UFM1 on the invasion and migration of gastric cancer cells were determined by the wound and trans-well assays, and the effect of UFM1 on subcutaneous tumor formation was verified in nude mice. The potential downstream targets of UFM1 and related molecular mechanisms were clarified by the human protein kinase assay and co-immunoprecipitation technique. Results Compared with the corresponding adjacent tissues, the transcription level and protein expression level of UFM1 in gastric cancer tissues were significantly downregulated (P < 0.05). The 5-year survival rate of gastric cancer patients with low UFM1 expression was significantly lower than the patients with high UFM1 expression (42.1% vs 63.0%, P < 0.05). The invasion and migration abilities of gastric cancer cells with stable UFM1 overexpression were significantly decreased, and the gastric cancer cells with UFM1 stable knockdown showed the opposite results; similar results were also obtained in the nude mouse model. Further studies have revealed that UFM1 could increase the ubiquitination level of PDK1 and decrease the expression of PDK1 at protein level, thereby inhibiting the phosphorylation level of AKT at Ser473. Additionally, the effect of UFM1 on gastric cancer cell function is dependent on the expression of PDK1. The expression level of UFM1 can improve the poor prognosis of PDK1 in patients with gastric cancer. Conclusion UFM1 suppresses the invasion and metastasis of gastric cancer by increasing the ubiquitination of PDK1 through negatively regulating PI3K/AKT signaling.

scholarly journals The molecular mechanisms of Aloin induce gastric cancer cells apoptosis by targeting High Mobility Group Box 1

2019 ◽  
Vol Volume 13 ◽  
pp. 1221-1231 ◽  
Author(s):  
Hong Tao ◽  
Tuo Tang ◽  
Shengnan Wang ◽  
Ziqian Wang ◽  
Yunfei Ma ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Molecular Mechanisms ◽  
High Mobility ◽  
High Mobility Group ◽  
Gastric Cancer Cells

Cellular and molecular mechanisms of the Ganoderma applanatum extracts induces apoptosis on SGC-7901 gastric cancer cells

2011 ◽  
Vol 29 (3) ◽  
pp. 175-182 ◽  
Author(s):  
Jieqiong Ma ◽  
Chanmin Liu ◽  
Yongqiang Chen ◽  
Jihong Jiang ◽  
Zhihong Qin
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Molecular Mechanisms ◽  
Gastric Cancer Cells ◽  
Ganoderma Applanatum

scholarly journals Cinnamaldehyde induces autophagy-mediated cell death through ER stress and epigenetic modification in gastric cancer cells

2021 ◽  
Author(s):  
Tae Woo Kim
Keyword(s):  
Gastric Cancer ◽  
Cell Death ◽  
Er Stress ◽  
Cancer Cells ◽  
Molecular Mechanisms ◽  
Epigenetic Modification ◽  
Autophagic Cell Death ◽  
Beclin 1 ◽  
Gastric Cancer Cells ◽  
Autophagy Inhibition

AbstractPrevious reports suggested that cinnamaldehyde (CA), the bioactive ingredient in Cinnamomum cassia, can suppress tumor growth, migratory, and invasive abilities. However, the role and molecular mechanisms of CA in GC are not completely understood. In the present study, we found that CA-induced ER stress and cell death via the PERK–CHOP axis and Ca2+ release in GC cells. Inhibition of ER stress using specific–siRNA blocked CA-induced cell death. Interestingly, CA treatment resulted in autophagic cell death by inducing Beclin-1, ATG5, and LC3B expression and by inhibiting p62 expression whereas autophagy inhibition suppressed CA-induced cell death. We showed that CA induces the inhibition of G9a and the activation of LC3B. Moreover, CA inhibited G9a binding on Beclin-1 and LC3B promoter. Overall, these results suggested that CA regulates the PERK–CHOP signaling, and G9a inhibition activates autophagic cell death via ER stress in GC cells.

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