Priming effect of aspirin for tumor cells to augment cytotoxic action of cisplatin against tumor cells: implication of altered constitution of tumor microenvironment, expression of cell cycle, apoptosis, and survival regulatory molecules

Hepatocellular carcinoma (HCC) is an aggressive cancer type with poor prognosis; thus, there is especially necessary and urgent to screen potential prognostic biomarkers for early diagnosis and novel therapeutic targets. In this study, we downloaded target data sets from the GEO database, and obtained codifferentially expressed genes using the limma R package and identified key genes through the protein–protein interaction network and molecular modules, and performed GO and KEGG pathway analyses for key genes via the clusterProfiler package and further determined their correlations with clinicopathological features using the Oncomine database. Survival analysis was completed in the GEPIA and the Kaplan–Meier plotter database. Finally, correlations between key genes, cell types infiltrated in the tumor microenvironment (TME), and hypoxic signatures were explored based on the TIMER database. From the results, 11 key genes related to the cell cycle were determined, and high levels of these key genes’ expression were focused on advanced and higher grade status HCC patients, as well as in samples of TP53 mutation and vascular invasion. Besides, the 11 key genes were significantly associated with poor prognosis of HCC and also were positively related to the infiltration level of MDSCs in the TME and the HIF1A and VEGFA of hypoxic signatures, but a negative correlation was found with endothelial cells (ECs) and hematopoietic stem cells. The result determined that 11 key genes (RRM2, NDC80, ECT2, CCNB1, ASPM, CDK1, PRC1, KIF20A, DTL, TOP2A, and PBK) could play a vital role in the pathogenesis of HCC, drive the communication between tumor cells and the TME, and act as probably promising diagnostic, therapeutic, and prognostic biomarkers in HCC patients.

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TRAIL targets cell cycle arrested tumor cells

Klinische Pädiatrie ◽

10.1055/s-0032-1310476 ◽

2012 ◽

Vol 224 (03) ◽

Author(s):

F Wachter ◽

M Grunert ◽

I Jeremias ◽

H Ehrhardt

Keyword(s):

Cell Cycle ◽

Tumor Cells

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Modulation of cell cycle progression by combined rapamycin-octreotide treatment in pituitary tumor cells

Experimental and Clinical Endocrinology & Diabetes ◽

10.1055/s-2007-990439 ◽

2007 ◽

Vol 115 (08) ◽

Author(s):

V Cerovac ◽

M Reimann ◽

GK Stalla ◽

M Theodoropoulou

Keyword(s):

Cell Cycle ◽

Tumor Cells ◽

Pituitary Tumor ◽

Cell Cycle Progression ◽

Cycle Progression ◽

Octreotide Treatment

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Antitumor Activity and Underlying Mechanism of Phomoxanthone B in MCF7 Cells

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520620999201124215511 ◽

2020 ◽

Vol 20 ◽

Author(s):

Chuan Chen ◽

Ziyue Zhao ◽

Qian Dong ◽

XueHui Gao ◽

Huibin Xu ◽

...

Keyword(s):

Breast Cancer ◽

Cell Cycle ◽

Antitumor Activity ◽

Oxidative Phosphorylation ◽

Tumor Cells ◽

Transcriptome Analysis ◽

Mcf7 Cells ◽

Er Positive ◽

Induced Apoptosis ◽

Positive Breast Cancer

Background:: Xanthones are a class of heterocyclic natural products, which are promising sources of anticancer leads. Phomoxanthone B（PXB）and Phomoxanthone A（PXA）are xanthone dimers. PXA is well studied as an anti-cancer agent, but PXB is not. In our study, PXB was isolated from the endophytic fungus Phomopsis sp. By254. Objective:: The purpose of this study was to identify the underlying anti-tumor mechanisms of PXB in breast cancer MCF7 cell line. Methods:: Apoptosis, cell cycle, proliferation, invasion and migration assays were used to assess the antitumor activity of PXB. RNA sequencing was used to analyze the effect of PXB treatment on gene expression in MCF7 cells. Results:: PXB showed cytotoxicity toward a variety of tumor cells, especially MCF7 cells. PXB inhibited the migration and invasion, arrested cell cycle at G2/M phase and induced apoptosis associated with caspase-3 activation in MCF7 cells. The detailed transcriptome analysis revealed that PXB affected several pathways related to tumorigenesis, metabolisms-, and oxidative phosphorylation in MCF7 cells. KEGG transcriptome analysis revealed that PXB upregulated pro-survival signal pathways such as MAPK, PI3K-AKT and STAT3 pathways. We found that PXB also significantly upregulated the expression of IL24, DDIT3 and XAF1, which may contribute to PXB-induced apoptosis. We further found that PXB may downregulate oxidative phosphorylation by decreasing the expression of electron transport chain genes, especially MT-ND1, which is a potential unfavorable prognostic marker for ER-positive breast cancer. Conclusion:: PXB exerts strong cytotoxicity against human tumor cells and has a potential for ER-positive breast cancer treatment.

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Attenuation of G 2 -Phase Cell Cycle Checkpoint Control Is Associated with Increased Frequencies of Unrejoined Chromosome Breaks in Human Tumor Cells

Radiation Research ◽

10.2307/3579585 ◽

1996 ◽

Vol 146 (2) ◽

pp. 139 ◽

Cited By ~ 7

Author(s):

Jeffrey L. Schwartz ◽

Janet Cowan ◽

David J. Grdina ◽

Ralph R. Weichselbaum

Keyword(s):

Cell Cycle ◽

Tumor Cells ◽

Human Tumor ◽

Cell Cycle Checkpoint ◽

Phase Cell ◽

Checkpoint Control ◽

Human Tumor Cells ◽

Chromosome Breaks ◽

Cycle Checkpoint

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Differentiated glioblastoma cells accelerate tumor progression by shaping the tumor microenvironment via CCN1-mediated macrophage infiltration

Acta Neuropathologica Communications ◽

10.1186/s40478-021-01124-7 ◽

2021 ◽

Vol 9 (1) ◽

Cited By ~ 2

Author(s):

Atsuhito Uneda ◽

Kazuhiko Kurozumi ◽

Atsushi Fujimura ◽

Kentaro Fujii ◽

Joji Ishida ◽

...

Keyword(s):

Tumor Microenvironment ◽

Tumor Progression ◽

Tumor Cells ◽

In Silico ◽

Tumor Tissue ◽

The Cancer Genome Atlas ◽

Macrophage Infiltration ◽

Macrophage Migration

AbstractGlioblastoma (GBM) is the most lethal primary brain tumor characterized by significant cellular heterogeneity, namely tumor cells, including GBM stem-like cells (GSCs) and differentiated GBM cells (DGCs), and non-tumor cells such as endothelial cells, vascular pericytes, macrophages, and other types of immune cells. GSCs are essential to drive tumor progression, whereas the biological roles of DGCs are largely unknown. In this study, we focused on the roles of DGCs in the tumor microenvironment. To this end, we extracted DGC-specific signature genes from transcriptomic profiles of matched pairs of in vitro GSC and DGC models. By evaluating the DGC signature using single cell data, we confirmed the presence of cell subpopulations emulated by in vitro culture models within a primary tumor. The DGC signature was correlated with the mesenchymal subtype and a poor prognosis in large GBM cohorts such as The Cancer Genome Atlas and Ivy Glioblastoma Atlas Project. In silico signaling pathway analysis suggested a role of DGCs in macrophage infiltration. Consistent with in silico findings, in vitro DGC models promoted macrophage migration. In vivo, coimplantation of DGCs and GSCs reduced the survival of tumor xenograft-bearing mice and increased macrophage infiltration into tumor tissue compared with transplantation of GSCs alone. DGCs exhibited a significant increase in YAP/TAZ/TEAD activity compared with GSCs. CCN1, a transcriptional target of YAP/TAZ, was selected from the DGC signature as a candidate secreted protein involved in macrophage recruitment. In fact, CCN1 was secreted abundantly from DGCs, but not GSCs. DGCs promoted macrophage migration in vitro and macrophage infiltration into tumor tissue in vivo through secretion of CCN1. Collectively, these results demonstrate that DGCs contribute to GSC-dependent tumor progression by shaping a mesenchymal microenvironment via CCN1-mediated macrophage infiltration. This study provides new insight into the complex GBM microenvironment consisting of heterogeneous cells.

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