Androgen attenuates antitumor effects of gastric cancer cells by bone marrow mesenchymal stem cells via restricting the JNK signaling activation
Linsong Mu, Wu Sui, Yang Lin, Wentao Yu, Hailong Su, Xiang Yu, Chengkun Qin
Journal:Translational Cancer Research
IF:1.07
DOI:10.21037/tcr.2019.06.04
PMID:35116831
Published:2019-06-01
research field:肿瘤学分子生物学细胞生物学消化生物学干细胞研究生物化学
Abstract
Background Researches on bone marrow mesenchymal stem cells (BMMSCs) have generated controversial results in tumor research. In the present study, we aimed to explore the functions of BMMSCs on gastric cancer and the possible mechanism in a mimicking microenvironment of the stomach. Methods Transwell co-cultured system was used to co-culture BMMSCs and gastric cancer SGC-7901 cells. In some experiments, androgen and its antagonist were added into the cells as required. Cell viability, cell apoptosis, mRNA and protein expressions of apoptosis- and JNK signaling- associated genes were respectively determined by performing cell counting kit-8, flow cytometry, quantitative real-time PCR and western blot. Results Androgen contributed to the growth of BMMSCs and SGC-7901 cells. In co-cultured system, BMMSCs not only suppressed SGC-7901 cell viability, induced cell apoptosis and promoted tumor necrosis factor (TNF)-α release, but also regulated the level of Bax/Bcl-2 and elevated the expressions of phosphorylation (p)-JNK and p53. After adding androgens, the anti-tumor effects of BMMSCs were weakened. Meanwhile, the antagonists of androgens could partially recover BMMSCs in vitro inhibitory effects on gastric cancer cells by activation of JNK signaling. Conclusions This study demonstrated the important roles of BMMSCs on the growth and apoptosis of gastric cancer cells in vitro . Additionally, in the mimicking microenvironment of the stomach, androgen weakened the antitumor effects of BMMSCs by limiting JNK signaling activation, suggesting that androgen antagonist may be a promising adjuvant drug to BMMSCs in gastric cancer therapy.
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