Sinapic acid inhibits pancreatic cancer proliferation, migration, and invasion via downregulation of the AKT /Gsk‐3β signal pathway

2021 ◽  
Author(s):  
Zhiwei Huang ◽  
Hao Chen ◽  
Peng Tan ◽  
Meizhou Huang ◽  
Hao Shi ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Sinapic Acid ◽  
Signal Pathway ◽  
Migration And Invasion ◽  
Cancer Proliferation ◽  
Gsk 3Β

scholarly journals β-Sitosterol and Gemcitabine Exhibit Synergistic Anti-pancreatic Cancer Activity by Modulating Apoptosis and Inhibiting Epithelial–Mesenchymal Transition by Deactivating Akt/GSK-3β Signaling

2019 ◽  
Vol 9 ◽  
Author(s):  
Zhang-qi Cao ◽  
Xue-xi Wang ◽  
Li Lu ◽  
Jing-wen Xu ◽  
Xiao-bin Li ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Epithelial Mesenchymal Transition ◽  
Human Cancer ◽  
Combined Treatment ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Gsk 3Β ◽  
Cancer Activity

β-sitosterol (BS), a major bioactive constituent present in plants, has shown potent anti-cancer activity against many human cancer cells, but its activity in pancreatic cancer (PC) cells has rarely been reported. Gemcitabine (GEM) is one of the first-line drugs for PC therapy, however, the treatment effect is not sustained due to prolonged drug resistance. In this study, we firstly studied the anti-PC activity and the mechanism of BS alone and in combination with GEM in vitro and in vivo. BS effectively inhibited the growth of PC cell lines by inhibiting proliferation, inducing G0/G1 phase arrest and apoptosis, suppressed the NF- kB activity, and increased expression of the protein Bax but decreased expression of the protein Bcl-2. Moreover, BS inhibited migration and invasion and downregulated epithelial–mesenchymal transition (EMT) markers and AKT/GSK-3β signaling pathways. Furthermore, the combination of BS and GEM exhibited a significant synergistic effect in MIAPaCa-2 and BXPC-3 cells. More importantly, the combined treatment with BS and GEM lead to significant growth inhibition of PC xenografts. Overall, our data revealed a promising treatment option for PC by the combination therapy of BS and GEM.

scholarly journals Isoalantolactone inhibits pancreatic cancer proliferation by regulation of PI3K and Wnt signal pathway

PLoS ONE ◽  
2021 ◽  
Vol 16 (3) ◽  
pp. e0247752
Author(s):  
Chaoxiong Zhang ◽  
Lei Huang ◽  
Jingyuan Xiong ◽  
Linshen Xie ◽  
Shi Ying ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Pancreatic Adenocarcinoma ◽  
Cell Lines ◽  
Signal Pathway ◽  
Cancer Proliferation ◽  
Adenocarcinoma Cell ◽  
Wnt Signal Pathway ◽  
Canonical Wnt ◽  
Wnt Signal

Background/aims Isoalantolactone (IATL) is one of multiple isomeric sesquiterpene lactones and is isolated from inula helenium. IATL has multiple functions such as antibacterial, antihelminthic and antiproliferative activities. IATL also inhibits pancreatic cancer proliferation and induces apoptosis by increasing ROS production. However, the detailed mechanism of IATL-mediated pancreatic cancer apoptosis remains largely unknown. Methods In current study, pancreatic carcinoma cell lines (PANC-1, AsPC-1, BxPC-3) and a mouse xenograft model were used to determine the mechanism of IATL-mediated toxic effects. Results IATL (20μM) inhibited pancreatic adenocarcinoma cell lines proliferation in a time-dependent way; while scratch assay showed that IATL significantly inhibited PANC-1 scratch closure (P<0.05); Invasion assays indicated that IATL significantly attenuated pancreatic adenocarcinoma cell lines invasion on matrigel. Signal analysis showed that IATL inhibited pancreatic adenocarcinoma cell proliferation by blocking EGF-PI3K-Skp2-Akt signal axis. Moreover, IATL induced pancreatic adenocarcinoma cell apoptosis by increasing cytosolic Caspase3 and Box expression. This apoptosis was mediated by inhibition of canonical wnt signal pathway. Finally, xenograft studies showed that IATL also significantly inhibited pancreatic adenocarcinoma cell proliferation and induced pancreatic adenocarcinoma cell apoptosis in vivo. Conclusions IATL inhibits pancreatic cancer proliferation and induces apoptosis on cellular and in vivo models. Signal pathway studies reveal that EGF-PI3K-Skp2-Akt signal axis and canonical wnt pathway are involved in IATL-mediated cellular proliferation inhibition and apoptosis. These studies indicate that IATL may provide a future potential therapy for pancreatic cancer.

scholarly journals The lncRNA RUNX1-IT1 regulates C-FOS transcription by interacting with RUNX1 in the process of pancreatic cancer proliferation, migration and invasion

2020 ◽  
Vol 11 (6) ◽  
Author(s):  
Songsong Liu ◽  
Junfeng Zhang ◽  
Liangyu Yin ◽  
Xianxing Wang ◽  
Yao Zheng ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Migration And Invasion ◽  
Cancer Proliferation

scholarly journals lncRNA-XLOC_012370 Promotes the Development of Pancreatic Cancer and Inactivates the NF-κB Pathway Through miR-140-5p

2021 ◽  
Vol 10 ◽  
Author(s):  
Han-Xiao Nie ◽  
Ling Zhang ◽  
Tao He ◽  
Li Wang ◽  
Bai-Shun Wan ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Progression ◽  
Malignant Tumors ◽  
Tumor Stage ◽  
Suppressor Gene ◽  
Signal Pathway ◽  
Regulatory Function ◽  
Migration And Invasion ◽  
Diagnostic Significance

Pancreatic cancer is a high incidence, high degree of malignancy, and high mortality in the digestive system tumor. The incidence of pancreatic cancer in China has increased nearly six folds in the past 20 years, ranking fifth in the mortality rate of malignant tumors, so it is particularly important to actively explore clinical indicators with better diagnostic significance for pancreatic cancer. LncRNA performs an essential regulatory function in the occurrence, development, and metastasis of many kinds of tumors, playing both a carcinogenic role and a tumor suppressor gene. Here, we demonstrated the function and mechanism of LncRNA-XLOC_012370 in the development of pancreatic cancer. In our research, the abnormal upregulation of XLOC_012370 was observed in pancreatic cancer patients’ tumor tissues. XLOC_012370 was related to tumor stage, lymph node metastasis, and overall survival. Silencing of XLOC_012370 prevented the proliferation, migration, and invasion via the NF-κB signal pathway. Further, miR-140-5p was identified as the target and downstream of XLOC_012370 and involved in pancreatic cancer progression. In vivo, knockdown of XLOC_012370 inhibited tumor growth via the NF-κB signal pathway. In conclusion, lncRNA-XLOC_012370 is closely related to some malignant clinicopathological features and prognosis of pancreatic cancer. Thus the miR-140-5p/NF-κB signal pathway might represent a promising treatment strategy to combat pancreatic cancer.

scholarly journals GSK-3β in Pancreatic Cancer: Spotlight on 9-ING-41, Its Therapeutic Potential and Immune Modulatory Properties

Biology ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 610
Author(s):  
Robin Park ◽  
Andrew L. Coveler ◽  
Ludimila Cavalcante ◽  
Anwaar Saeed
Keyword(s):  
Pancreatic Cancer ◽  
Therapeutic Potential ◽  
Glycogen Synthase ◽  
Glycogen Synthase Kinase ◽  
Glycogen Synthase Kinase 3 ◽  
In Vivo Models ◽  
Gsk 3Β ◽  
Early Phase Clinical Trials

Glycogen synthase kinase-3 beta is a ubiquitously and constitutively expressed molecule with pleiotropic function. It acts as a protooncogene in the development of several solid tumors including pancreatic cancer through its involvement in various cellular processes including cell proliferation, survival, invasion and metastasis, as well as autophagy. Furthermore, the level of aberrant glycogen synthase kinase-3 beta expression in the nucleus is inversely correlated with tumor differentiation and survival in both in vitro and in vivo models of pancreatic cancer. Small molecule inhibitors of glycogen synthase kinase-3 beta have demonstrated therapeutic potential in pre-clinical models and are currently being evaluated in early phase clinical trials involving pancreatic cancer patients with interim results showing favorable results. Moreover, recent studies support a rationale for the combination of glycogen synthase kinase-3 beta inhibitors with chemotherapy and immunotherapy, warranting the evaluation of novel combination regimens in the future.

scholarly journals CHN1 promotes epithelial–mesenchymal transition via the Akt/GSK-3β/Snail pathway in cervical carcinoma

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Haoqi Zhao ◽  
Lan Wang ◽  
Shufang Wang ◽  
Xihua Chen ◽  
Min Liang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Lymph Node ◽  
Signaling Pathway ◽  
Cervical Carcinoma ◽  
Epithelial Mesenchymal Transition ◽  
Migration And Invasion ◽  
Xenograft Tumor ◽  
Mesenchymal Transition ◽  
Gsk 3Β ◽  
Related Proteins

Abstract Background Metastasis and invasion are crucial in determining the mortality of cervical carcinoma (CC) patients. The epithelial–mesenchymal transition (EMT) is now a universal explanation for the mechanisms of tumor metastasis. Α-chimeric protein (α-chimaerin, CHN1) plays an important role in the regulation of signal transduction and development. However, the molecular regulatory relationships between CHN1 and CC progression in relation to EMT have not yet been identified. Methods The expression of CHN1 in CC tissues, adjacent tissues, and lymph node metastases from CC patients was detected by immunohistochemistry. Upregulation and knockdown of CHN1 were achieved by transfection of CC cells. The effect of CHN1 on cell proliferation was determined by CCK-8 and plate clone formation assays. Changes in migration and invasion capabilities were evaluated using scratch migration and transwell invasion assays. The effect of CHN1 overexpression and interference on xenograft tumor growth was determined by tumor weight and pathological analyses. The expression of EMT-related mRNAs was measured by qRT-PCR in transfected CC cells. EMT-related proteins and Akt/GSK-3β/Snail signaling pathway-related proteins were also evaluated by western blotting. Results CHN1 was overexpressed in CC tissues and was associated with lymph node metastasis and low survival in CC patients. Overexpression of CHN1 promoted cell proliferation, migration, and invasion in CC cells. In contrast, silencing of CHN1 inhibited these phenomena. Overexpression of CHN1 promoted tumor formation in an in vivo xenograft tumor mouse model, with increased tumor volumes and weights. In addition, CHN1 induced the expression of EMT-related transcription factors, accompanied by the decreased expression of epithelial markers and increased expression of mesenchymal markers. The Akt/GSK-3β/Snail signaling pathway was activated by overexpression of CHN1 in vitro, and activation of this pathway was inhibited by the signaling pathway inhibitor LY294002. Conclusion These results suggest that CHN1 promotes the development and progression of cervical carcinoma via the Akt/GSK-3β/Snail pathway by inducing EMT.

Sign in / Sign up

Export Citation Format

Share Document