scholarly journals Solasodine, Isolated from Solanum sisymbriifolium Fruits, Has a Potent Anti-Tumor Activity Against Pancreatic Cancer

2021 ◽  
Vol Volume 15 ◽  
pp. 1509-1519
Author(s):  
Yingchao Fan ◽  
Zhumeng Li ◽  
Liting Wu ◽  
Feng Lin ◽  
Jinfeng Shao ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Anti Tumor Activity ◽  
Solanum Sisymbriifolium

Evaluation of a nonbiologic nanoparticle form of paclitaxel in metastatic pancreatic cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e15076-e15076 ◽  
Author(s):  
Kouros Motamed ◽  
Larn Hwang ◽  
Chao Hsiao ◽  
Vuong N. Trieu
Keyword(s):  
Pancreatic Cancer ◽  
Phase I ◽  
Cell Lines ◽  
Advanced Pancreatic Cancer ◽  
Metastatic Pancreatic Cancer ◽  
In Vitro Toxicity ◽  
Pancreatic Cell ◽  
Anti Tumor Activity

e15076 Background: The (nab-Pac)/Gemcitabine (Gem) combination has recently been shown to impart a significant survival advantage over Gem alone in patients with metastatic pancreatic cancer. The goal of this study was to define a non-biologic, nanoparticle paclitaxel (NBN-Pac) which has a similar toxicity profile and utilizes the same albumin-mediated transport mechanism. Herein, we report in vitro, preclinical and phase I clinical results for this NBN-Pac in metastatic pancreatic cancer. Methods: In vitro drug cytotoxicity was measured as mean IC50 values following a 72-h exposure in four pancreatic cell lines (MIA Paca-2 and Capan-1 and multi-drug resistant cell lines PANC-1 and ASPC-1). In vivo anti-tumor activities were assessed in xenografted MIA PaCa-2 and PANC-1 models in nude mice treated with three i.v. doses of NBN-Pac (20, 50 mg/kg) and Taxol (20 mg/kg) on days 0, 3, and 6 (q3dx3), and twelve i.v. doses of Gem (140 mg/kg) on every 3 days (q3dx12). A phase I clinical trial (N=18) was conducted to determine the MTD and the recommended phase II dose of the combination therapy with NBN-Pac (220-300 mg/m2, q3w) and Gem (1250 mg/m2) as primary endpoints in first line treatment of subjects with advanced pancreatic cancer. Reduction in the plasma levels of CA19-9 was measured as a PD biomarker. Results: The mean IC50 value of NBN-Pac in four pancreatic cell lines was approximately 30-fold lower than that of Gem. NBN-Pac formulation (50 mg/kg) produced superior anti-tumor activity in the two xenograft models tested over Taxol and Gem at clinically equivalent doses. Our phase I trial established the MTD of this NBN-Pac formulation as 300mg/m2. Moreover, 5 out of 16 subjects (31.3%) were CR or PR with 95% exact confidence interval of (11.0%, 58.7%). The median PFS time was 5.6 month (95% C.I = 2.9). The median OS time could not be estimated as the survival rate did not fall below 50%. Other safety variables revealed no significant abnormality that may have affected the result of the study. Conclusions: NBN-Paclitaxel formulation has superior anti-tumor activity vs. Taxol and Gem in in vitro toxicity assays, preclinical models of pancreatic cancer, as well in a phase I clinical study in patients with advanced pancreatic cancer.

scholarly journals Nigericin Suppresses the Wnt/β-catenin Signaling in Pancreatic Cancer through Targeting pre-miR-374b-PRKCA/HBP1 Axis

2020 ◽  
Author(s):  
Qiaoming Zhi ◽  
Wei Li ◽  
Dongming Zhu ◽  
Daiwei Wan ◽  
Ye Han ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Tumor Model ◽  
Migration And Invasion ◽  
Inhibitory Effects ◽  
Biochemical Basis ◽  
Over Expression ◽  
Anti Cancer ◽  
Ic50 Values ◽  
Anti Tumor Activity

Abstract Background The polyether antibiotic nigericin has been demonstrated recently to have anti-tumor activity in multiple cancers. But the biochemical basis for its anti-cancer effects has not been fully elucidated. The objective of this study was to investigate the potential mechanisms of nigericin in pancreatic cancer (PC) cells. Methods PC cells were exposed to increasing concentrations of nigericin at different time periods, and the corresponding IC50 values were calculated. Then the effects on the biological functions of PC cells were evaluated. Subsequent experiments including the high-throughput RNA sequencing, qRT-PCR, western blot, TOP/FOP-Flash reporter, Co-Immunoprecipitation and luciferase report assays were employed to reveal the potential mechanisms of nigericin. In addition, the inhibitory effects of nigericin on PC cells were also accessed in the subcutaneous tumor model. Results The data showed that nigericin was extremely sensitive to PC cells, and could influence the abilities of cell proliferation, colony formation, apoptosis, migration and invasion. The results in vitro implied that nigericin suppressed the Wnt/β-catenin signaling by up-regulating PRKCA and HBP1 mRNA expressions. Furthermore, the dual strands of pre-miR-374b were proved to down-regulate the PRKCA and HBP1 expressions coordinately, and over-expression of pre-miR-374b partly antagonized the suppressing effects of PC cells induced by nigericin. Meanwhile, the inhibitory effects of nigericin on PC cells were also confirmed in mice. Conclusion These findings demonstrated that suppressing the Wnt/β-catenin signaling pathway by targeting pre-miR-374b-PRKCA/HBP1 axis might represent a novel molecular mechanism of nigericin in PC. Nigericin remained a candidate for a potential pre-clinical application for PC.

Abstract 4505: Anti-tumor activity in pancreatic cancer of a low immunogenic and clinically optimized anti-mesothelin immunotoxin RG7787

2014 ◽  
Author(s):  
Ira Pastan ◽  
Kevin Hollevoet ◽  
Emily Mason-Osann ◽  
Christine Alewine ◽  
Xiu-Fen Liu
Keyword(s):  
Pancreatic Cancer ◽  
Anti Tumor Activity

Synthesis, characterization and anti-tumor activity of novel thymoquinone analogs against pancreatic cancer

2013 ◽  
Vol 23 (10) ◽  
pp. 3101-3104 ◽  
Author(s):  
Mujahid Yusufi ◽  
Sanjeev Banerjee ◽  
Momin Mohammad ◽  
Sandhya Khatal ◽  
K. Venkateswara Swamy ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Anti Tumor Activity

scholarly journals Oridonin enhances the anti-tumor activity of gemcitabine towards pancreatic cancer by stimulating Bax- and Smac-dependent apoptosis

2020 ◽  
Vol 9 (7) ◽  
pp. 4148-4161
Author(s):  
Dian-Lei Liu ◽  
He-Qi Bu ◽  
Wen-Long Wang ◽  
Hua Luo ◽  
Bo-Ning Cheng
Keyword(s):  
Pancreatic Cancer ◽  
Anti Tumor Activity

scholarly journals The Anti-Dysenteric Drug Fraxetin Enhances Anti-Tumor Efficacy of Gemcitabine and Suppresses Pancreatic Cancer Development by Antagonizing STAT3 Activation

2020 ◽  
Author(s):  
Yangyang Guo ◽  
Yanyi Xiao ◽  
Hangcheng Guo ◽  
Hengyue Zhu ◽  
Dong Chen ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Glucose Metabolism ◽  
Mouse Models ◽  
Sh2 Domain ◽  
Cancer Development ◽  
Migration And Invasion ◽  
Signal Pathways ◽  
Mesenchymal Transition ◽  
Pancreatic Cancer Cells ◽  
Anti Tumor Activity

Abstract BackgroundFraxetin, a natural product isolated and purified from the bark of Fraxinus bungeana A.DC., has anti-inflammatory, analgesic and anti-dysenteric activities. This study aimed to investigate the anti-tumor effects of fraxetin in pancreatic ductal adenocarcinoma (PDA) and elucidate the underlying molecular mechanism. MethodsThe effects of quercetin on the proliferation, apoptosis, migration and invasion of pancreatic cancer cells (PCCs), and tumor growth and metastasis in PDA xenograft mouse models were evaluated. Besides, the effects of fraxetin on the sensitivity of PCCs to gemcitabine were evaluated. Moreover, angiogenesis, glucose metabolism, the epithelial-mesenchymal transition (EMT), reactive oxygen species (ROS), and STAT3 activity were analyzed.ResultsIn PCCs, fraxetin inhibited the proliferation, induced mitochondrial-dependent apoptosis, and suppressed the invasion and migration by reversing the EMT. In nude mouse models, PDA growth and metastasis were reduced by fraxetin treatment. Moreover, fraxetin enhanced the sensitivity of PCCs to the chemotherapy drug gemcitabine. Mechanically, oncogenic KRAS-triggered STAT3 activation in PCCs and PDA tissues was suppressed by fraxetin treatment. Fraxetin shows important interactions with STAT3 Src Homology 2 (SH2) domain residues to occupy the pTyr‐recognition site of its SH2 domain of another STAT3 monomer, thereby preventing its homo-dimer formation, which then blocks the activation of downstream signal pathways. The anti-tumor activity of fraxetin in PDA was functionally rescued by a STAT3 activator colivelin. As a result, fraxetin hindered hypoxia-induced angiogenesis by decreasing HIF-1α and VEGFA expression, controlled glucose metabolism by reducing GLUT1 expression, inhibited the EMT by blocking the Slug-E-cadherin axis, and drove ROS-mediated apoptosis by regulating STAT3-Ref1 axis.ConclusionThese findings indicate that fraxetin enhances anti-tumor activity of gemcitabine and suppresses pancreatic cancer development by antagonizing STAT3 activation.

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