Androgen attenuates antitumor effects of gastric cancer cells by bone marrow mesenchymal stem cells via restricting the JNK signaling activation

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.

Oridonin induces autophagy-mediated cell death in pancreatic cancer by activating the c-Jun N-terminal kinase pathway and inhibiting phosphoinositide 3-kinase signaling

“…The involvement of MAPKs in multiple physiological and pathological processes has been evidenced by a growing bank of research (48). JNK, a stress-responsive kinase, is closely related to cell growth, differentiation, apoptosis, tumorigenesis, and other signaling pathways (49,50). At the molecular level, oridonin is a bioactive diterpenoid isolated from Rabdosia rubescens.…”

Healing of bone defects by induced pluripotent stem cell-derived bone marrow mesenchymal stem cells seeded on hydroxyapatite-zirconia

“…However, the acquisition of MSCs, such as BMSCs, requires bone marrow extraction, which often causes great pain to patients. The number of BMSCs is very small, with only one BMSC per 100,000 nucleated cells in bone marrow (4,5). Contrastingly, iPSCs are derived from reprogramming of somatic cells and have strong self-renewal, proliferation, and differentiation capabilities similar to ESCs.…”