scholarly journals Traditional Chinese medicine Astragalus polysaccharide enhanced antitumor effects of the angiogenesis inhibitor apatinib in pancreatic cancer cells on proliferation, invasiveness, and apoptosis

2018 ◽  
Vol Volume 11 ◽  
pp. 2685-2698 ◽  
Author(s):  
Jun Wu ◽  
Jing Wang ◽  
Qiang Su ◽  
Wei Ding ◽  
Teng Li ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Cancer Cells ◽  
Angiogenesis Inhibitor ◽  
Antitumor Effects ◽  
Pancreatic Cancer Cells

Bufalin exerts antitumor effects by inducing cell cycle arrest and triggering apoptosis in pancreatic cancer cells

Tumor Biology ◽  
2013 ◽  
Vol 35 (3) ◽  
pp. 2461-2471 ◽  
Author(s):  
Meiying Li ◽  
Xuejun Yu ◽  
Hui Guo ◽  
Limei Sun ◽  
Aijun Wang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Pancreatic Cancer ◽  
Cell Cycle Arrest ◽  
Cancer Cells ◽  
Antitumor Effects ◽  
Cycle Arrest ◽  
Pancreatic Cancer Cells

Studying Antitumor Effects of Sirna Gene Silencing of some Metabolic Genes in Pancreatic Ductal Adenocarcinoma

2020 ◽  
Vol 13 ◽  
Author(s):  
Ahmad Sada Al hanjori ◽  
Walhan Alshaer ◽  
Bayan Anati ◽  
Suha Wehaibi ◽  
Malek Zihlif
Keyword(s):  
Pancreatic Cancer ◽  
Cell Proliferation ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Cancer Cells ◽  
Cell Line ◽  
Pentose Phosphate ◽  
Ductal Adenocarcinoma ◽  
Maximum Effect ◽  
Antitumor Effects ◽  
Pancreatic Cancer Cells

Background: Earlier diagnosis and advances in treatment strategies have increased the average survival of cancer patients over the last decades. Despite the increased number of new anti-neoplastic agents, there has been no adequate therapy for intricate malignancies such as pancreatic cancer. Cancer metabolism is the main building block standing behind cancer promotion and progression even in the presence of a harsh environment. Targeting metabolic pathways, such as glycolysis and pentose phosphate pathway, is regarded as a promising new strategy for cancer treatment. Objective: The current study is to investigate the effect of knocking-down pancreatic cancer glycolytic and pentose phosphate pathway's regulators (HIF-1α, ARNT, PFKFB4, and RBKS), on cell’s viability and resistance to gemcitabine and doxorubicin, using small interference RNA. Methodology: The human pancreatic ductal adenocarcinoma cell line, Panc-1, was used to study the anti-proliferative activity of targeting HIF-1α, ARNT, PFKFB4, and RBKS mRNAs by transfection with small interference RNAs, each one alone and in combination. The transfected cells were also treated with doxorubicin and gemcitabine to study the relationship between the concerned genes and the resistance of Panc-1 cells to these drugs. The effect on cell proliferation was determined using a colorimetric assay and Inhibitory Concentration (IC50) calculation. A cross-talk study was done to investigate the silencing effect of one of the above genes on the expression of others using Real Time-Polymerase Chain Reaction. Results: In vitro transfection with small interference-RNAs, siHIF-1α, siPFKFB4, and siARNT decreased tumor cell proliferation with a maximum effect shown with siPFKFB4; but there was no anti-proliferative effect with RBKS silencing. suppression of transcription of HIF-1α, ARNT, PFKFB4, and RBKS sensitize pancreatic cancer cells, Panc-1, to doxorubicin and gemcitabine. Conclusion: This study demonstrated the major tumor promoting and progressive effects of PFKFB4, while HIF-1α and ARNT had modulator effects in pancreatic cancer cells (Panc-1). RBKS had a chemo-resistant role justifying its enhanced expression in Panc-1 cells, but not a proliferative one. Silencing of all genes of interest decreased doxorubicin and gemcitabine's resistance and improved the antitumor effect of doxorubicin and gemcitabine in the pancreatic cancer cell line, Panc-1.

scholarly journals The Antitumor Efficacy of β-Elemene by Changing Tumor Inflammatory Environment and Tumor Microenvironment

2020 ◽  
Vol 2020 ◽  
pp. 1-13 ◽  
Author(s):  
Qiang Xie ◽  
Fengzhou Li ◽  
Lei Fang ◽  
Wenzhi Liu ◽  
Chundong Gu
Keyword(s):  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Cancer Cells ◽  
Traditional Chinese Medicines ◽  
Active Ingredients ◽  
Antitumor Effects ◽  
Tumor Immune Escape ◽  
Chinese Medicines ◽  
Inflammatory Microenvironment ◽  
Anti Inflammatory

Inflammatory mediators and inflammatory cells in the inflammatory microenvironment promote the transformation of normal cells to cancer cells in the early stage of cancer, promote the growth and development of cancer cells, and induce tumor immune escape. The monomeric active ingredient β-elemene is extracted from the traditional Chinese medicine Curcuma wenyujin and has been proven to have good anti-inflammatory and antitumor activities in clinical applications for more than 20 years in China. Recent studies have found that this traditional Chinese medicine plays a vital role in macrophage infiltration and M2 polarization, as well as in regulating immune disorders, and it even regulates the transcription factors NF-κB and STAT3 to alter inflammation, tumorigenesis, and development. In addition, β-elemene regulates not only different inflammatory factors (such as TNF-α, IFN, TGF-β, and IL-6/10) but also oxidative stress in vivo and in vitro. The excellent anti-inflammatory and antitumor effects of β-elemene and its ability to alter the inflammatory microenvironment of tumors have been gradually elaborated. Although the study of monomeric active ingredients in traditional Chinese medicines is insufficient in terms of quality and quantity, the pharmacological effects of more active ingredients of traditional Chinese medicines will be revealed after β-elemene.

scholarly journals Disulfiram Alone Functions as a Radiosensitizer for Pancreatic Cancer Both In Vitro and In Vivo

2021 ◽  
Vol 11 ◽  
Author(s):  
Ying Xu ◽  
Lunjie Lu ◽  
Judong Luo ◽  
Lili Wang ◽  
Qi Zhang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Copper Ions ◽  
Dna Double Strand Breaks ◽  
Antitumor Effects ◽  
Pancreatic Cancer Cells ◽  
M Phase

The prognosis of pancreatic cancer remains very poor worldwide, partly due to the lack of specificity of early symptoms and innate resistance to chemo-/radiotherapy. Disulfiram (DSF), an anti-alcoholism drug widely used in the clinic, has been known for decades for its antitumor effects when simultaneously applied with copper ions, including pancreatic cancer. However, controversy still exists in the context of the antitumor effects of DSF alone in pancreatic cancer and related mechanisms, especially in its potential roles as a sensitizer for cancer radiotherapy. In the present study, we focused on whether and how DSF could facilitate ionizing radiation (IR) to eliminate pancreatic cancer. DSF alone significantly suppressed the survival of pancreatic cancer cells after exposure to IR, both in vitro and in vivo. Additionally, DSF treatment alone caused DNA double-strand breaks (DSBs) and further enhanced IR-induced DSBs in pancreatic cancer cells. In addition, DSF alone boosted IR-induced cell cycle G2/M phase arrest and apoptosis in pancreatic cancer exposed to IR. RNA sequencing and bioinformatics analysis results suggested that DSF could trigger cell adhesion molecule (CAM) signaling, which might be involved in its function in regulating the radiosensitivity of pancreatic cancer cells. In conclusion, we suggest that DSF alone may function as a radiosensitizer for pancreatic cancer, probably by regulating IR-induced DNA damage, cell cycle arrest and apoptosis, at least partially through the CAM signaling pathway.

scholarly journals Histone acetyltransferase 1 promotes gemcitabine resistance by regulating the PVT1/EZH2 complex in pancreatic cancer

2021 ◽  
Vol 12 (10) ◽  
Author(s):  
Yan Sun ◽  
Dianyun Ren ◽  
Yingke Zhou ◽  
Jian Shen ◽  
Heshui Wu ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Noncoding Rna ◽  
Histone Acetyltransferase ◽  
Resistance Mechanisms ◽  
Antitumor Effects ◽  
Gemcitabine Resistance ◽  
Pancreatic Cancer Cells

AbstractThe poor prognosis of pancreatic cancer is primarily due to the development of resistance to therapies, including gemcitabine. The long noncoding RNA PVT1 (lncRNA PVT1) has been shown to interact with enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2), promoting gemcitabine resistance in pancreatic cancer. In this study, we found histone acetyltransferase 1 (HAT1) enhanced the tolerance of pancreatic cancer cells to gemcitabine and HAT1-mediated resistance mechanisms were regulated by PVT1 and EZH2. Our results showed that the aberrant HAT1 expression promoted gemcitabine resistance, while silencing HAT1 restored gemcitabine sensitivity. Moreover, HAT1 depletion caused a notable increase of gemcitabine sensitivity in gemcitabine-resistant pancreatic cancer cell lines. Further research found that HAT1 increased PVT1 expression to induce gemcitabine resistance, which enhanced the binding of bromodomain containing 4 (BRD4) to the PVT1 promoter, thereby promoting PVT1 transcription. Besides, HAT1 prevented EZH2 degradation by interfering with ubiquitin protein ligase E3 component n-recognin 4 (UBR4) binding to the N-terminal domain of EZH2, thus maintaining EZH2 protein stability to elevate the level of EZH2 protein, which also promoted HAT1-mediated gemcitabine resistance. These results suggested that HAT1 induced gemcitabine resistance of pancreatic cancer cells through regulating PVT1/EZH2 complex. Given this, Chitosan (CS)-tripolyphosphate (TPP)-siHAT1 nanoparticles were developed to block HAT1 expression and improve the antitumor effect of gemcitabine. The results showed that CS-TPP-siHAT1 nanoparticles augmented the antitumor effects of gemcitabine in vitro and in vivo. In conclusion, HAT1-targeted therapy can improve observably gemcitabine sensitivity of pancreatic cancer cells. HAT1 is a promising therapeutic target for pancreatic cancer.

Transcription factor Sp1 is upregulated by PKCι to drive the expression of YAP1 during pancreatic carcinogenesis

2020 ◽  
Author(s):  
Jinhe Yang ◽  
Junli Wang ◽  
Hongmei Zhang ◽  
Changlong Li ◽  
Changyan Chen ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Transcription Factor ◽  
Cancer Cells ◽  
Synergistic Effects ◽  
Pancreatic Tumors ◽  
Antitumor Effects ◽  
Pancreatic Cancer Cells ◽  
Factor Specificity ◽  
Underlying Mechanisms ◽  
Specificity Protein

Abstract Recently, we identified that the atypical protein kinase C isoform ι (PKCι) enhances the expression of YAP1 to promote the tumorigenesis of pancreatic adenocarcinoma harboring mutant KRAS (mu-KRAS). To advance our understanding about underlying mechanisms, we analyze the transcription of YAP1 in pancreatic cancer cells and reveal that transcription factor Specificity Protein 1 (Sp1) is upregulated by PKCι and subsequently binds to multiple sites in YAP1 promoter to drive the transactivation of YAP1 in pancreatic cancer cells carrying mu-KRAS. The bioinformatics analysis further substantiates that the expression of PKCι, Sp1 and YAP1 is correlated and associated with the stages and prognosis of pancreatic tumors. Moreover, our apoptotic detection data demonstrate that combination of PKCι and Sp1 inhibitors at subtoxic doses displays synergistic effects on inducing apoptosis and reversing the immunosuppression of pancreatic cancer cells, establishing the combination of PKCι and Sp1 inhibitors as a promising novel therapeutic approach, or an adjuvant strategy to potentiate the antitumor effects of other immunotherapeutic agents in pancreatic cancer treatment.

scholarly journals Inhibition of miR-222 by Oncolytic Adenovirus-Encoded miRNA Sponges Promotes Viral Oncolysis and Elicits Antitumor Effects in Pancreatic Cancer Models

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3233
Author(s):  
Giulia Raimondi ◽  
Sabrina Gea-Sorlí ◽  
Marc Otero-Mateo ◽  
Cristina Fillat
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Genetic Alterations ◽  
Oncolytic Adenovirus ◽  
Viral Fitness ◽  
Host Cells ◽  
Antitumor Effects ◽  
Pancreatic Cancer Cells ◽  
Cellular Environment ◽  
Viral Yield

Oncolytic adenoviruses (OA) are envisioned as a therapeutic option for patients with cancer, designed to preferentially replicate in cancer cells. However, the high number of genetic alterations in tumors can generate a context in which adenoviruses have difficulties replicating. Abnormal miRNAs expression is a trademark of pancreatic cancer, with several oncogenic miRNAs playing essential roles in cancer-associated pathways. The perturbed miRNome induces reprogramming of gene expression in host cells that can impact the complex interplay between cellular processes and viral replication. We have studied the effects of overexpressed miRNAs on oncolytic adenoviral activity and identified miRNAs modulators of adenoviral oncolysis in pancreatic cancer cells. Inhibition of the highly upregulated miR-222 sensitized cancer cells to oncolysis. To provide a therapeutic application to this insight, we engineered the oncolytic adenovirus AdNuPARmE1A with miR-222 binding sites, working as sponges to withdraw the miRNA from the cellular environment. AdNuPAR-E-miR222-S mediated-decrease of miR-222 expression in pancreatic cancer cells strongly improved the viral yield and enhanced the adenoviral cytotoxic effects. Antitumoral studies confirmed a high activity for AdNuPARmE1A-miR222-S in vivo, controlling tumor progression more effectively than the scrambled control virus in xenografts. We demonstrated that the increased antitumor potency of the novel oncolytic virus resulted from the combinatory effects of miR-222 oncomiR inhibition and the restoration of miR-222 target genes activity enhancing viral fitness.

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