AB237. Human adipose derived stem cells induced cell apoptosis and S phase arrest in bladder tumor

Background: Mesenchymal stem cells (MSCs) had received much attention in recent years owing to their capacity to differentiate intaao many other cell types. Currently a lot of studies found that MSCs could secrete cytokines and chemokines which affect the growth of tumor cells. Adipose derived mesenchymal stem cells (ADSCs) could differentiate into a variety of different cells as well which were available easier. They could affect the growth of tumor cells, but the mechanism was not clear. We were trying to investigate their effect on bladder cancer cells growth to illustrate the possible mechanisms.

Methods: Transwell chamber co-culture was used to observe the effect of ADSCs on bladder cancer cell line T24 and EJ growth. T24 and EJ cells were cultured with condition medium of ADSCs and then recorded tumor cell activity by MTS assay. We used AnnexinV-PI double staining for tumor cell apoptosis, colony formation assay for tumor cell proliferation, wound healing for tumor cell migration, western blot for 5 detecting tumor cell associated protein expressing and molecular signaling pathways.

Results: The cell counting and colony formation assay showed ADSCs inhibited the proliferation of EJ and T24 cells. Cell viability assessment revealed that the secretions, in the form of conditioned medium, were able to decrease cancer cell viability. Wound-healing assay suggested ADSCs suppressed migration of T24 and EJ cells. Moreover, the results of the flow cytometry indicated that ADSCs were capable of inducing apoptosis of T24 cells and inducing S phase cell cycle arrest. Western blot revealed ADSCs increased the expression of cleaved Caspase-3 and cleaved PARP, indicating that ADSCs induced apoptosis in a caspase-dependent way. PTEN/PI3K/Akt pathway and Bcl-2 family proteins were involved in the mechanism of this reaction.

Conclusions: For the first time, we have provided the evidence to prove that ADSCs could obviously inhibit the proliferation of bladder cancer cells through apoptosis. The antiproliferative effect of ADSCs on bladder cancer cells appears to be mediated by the secretion of soluble factors which are involved in the PTEN/PI3K/Akt signaling pathway. Since ADSCs can be easily obtained as a stem cell source without ethical concerns and can be amplified quickly, ADSCs may provide a promising and practicable manner for bladder cancer therapy. However, further in vivo studies are needed to provide a more comprehensive insight into its antitumor effect.

Keywords: Adipose derived mesenchymal stem cells (ADSCs); bladder tumor; apoptosis; Akt