DT-13 synergistically potentiates the sensitivity of gastric cancer cells to topotecan via cell cycle arrest in vitro and in vivo

Objective. The aim of this study was to investigate the in vitro antitumor effects of Nidus Vespae on gastric cancer and its ability to promote immune function. Methods. Cell viability was detected by the Cell Counting Kit-8 (CCK-8) assay. Cell cycle distribution and apoptosis were detected using flow cytometry. The THP-1 human monocytic cell line was used as a source of monocytic effector cells for analyzing proliferation and dendritic cell (DC) induction. Enzyme-linked immunosorbent assay was used to detect cytokine production, and multicolor flow cytometry was used to study the phenotype and functionality of THP-1 DCs. Results. A high concentration (>10 mg/mL) of Nidus Vespae decoction (NVD) inhibited SGC-7901 gastric cancer cell growth by inducing G2/M cell cycle arrest and apoptosis. However, a low concentration (≤10 mg/mL) of NVD significantly increased the proliferative ability of THP-1 in serum-containing medium and caused an increase in dendritic protrusions with the typical morphology of DCs compared to the negative control in serum-free medium. The THP-1 DCs had significantly increased expression of cluster of differentiation 11c (CD11c), CD40, CD80, CD83, and CD86, as well as secretion of tumor necrosis factor-alpha. Furthermore, the supernatant of THP-1 DCs significantly inhibited the proliferation of gastric cancer cells by inducing apoptosis and G1/S cell cycle arrest. Conclusions. Our findings suggest that NVD not only directly inhibits the growth of gastric cancer cells but also exerts indirect antitumor effects by enhancing immune function. These results provide an important theoretical basis for the clinical application of Nidus Vespae in gastric cancer treatment.

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Menadione reduces CDC25B expression and promotes tumor shrinkage in gastric cancer

Therapeutic Advances in Gastroenterology ◽

10.1177/1756284819895435 ◽

2020 ◽

Vol 13 ◽

pp. 175628481989543

Author(s):

Amanda Braga Bona ◽

Danielle Queiroz Calcagno ◽

Helem Ferreira Ribeiro ◽

José Augusto Pereira Carneiro Muniz ◽

Giovanny Rebouças Pinto ◽

...

Keyword(s):

Gastric Cancer ◽

Cell Cycle ◽

Cell Cycle Arrest ◽

Cell Lines ◽

Specific Inhibitor ◽

Gastric Carcinogenesis ◽

In Vivo Experiments ◽

Cycle Arrest

Background: Gastric cancer is one of the most incident types of cancer worldwide and presents high mortality rates and poor prognosis. MYC oncogene overexpression is a key event in gastric carcinogenesis and it is known that its protein positively regulates CDC25B expression which, in turn, plays an essential role in the cell division cycle progression. Menadione is a synthetic form of vitamin K that acts as a specific inhibitor of the CDC25 family of phosphatases. Methods: To better understand the menadione mechanism of action in gastric cancer, we evaluated its molecular and cellular effects in cell lines and in Sapajus apella, nonhuman primates from the new world which had gastric carcinogenesis induced by N-Methyl-N-nitrosourea. We tested CDC25B expression by western blot and RT-qPCR. In-vitro assays include proliferation, migration, invasion and flow cytometry to analyze cell cycle arrest. In in-vivo experiments, in addition to the expression analyses, we followed the preneoplastic lesions and the tumor progression by ultrasonography, endoscopy, biopsies, histopathology and immunohistochemistry. Results: Our tests demonstrated menadione reducing CDC25B expression in vivo and in vitro. It was able to reduce migration, invasion and proliferation rates, and induce cell cycle arrest in gastric cancer cell lines. Moreover, our in-vivo experiments demonstrated menadione inhibiting tumor development and progression. Conclusions: We suggest this compound may be an important ally of chemotherapeutics in the treatment of gastric cancer. In addition, CDC25B has proven to be an effective target for investigation and development of new therapeutic strategies for this malignancy.

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