Pretreatment of BMSCs with TZD solution decreases the proliferation rate of MCF-7 cells by reducing FGF4 protein expression

Abstract

The present study aimed to investigate the effects of bone marrow-derived mesenchymal stem cells (BMSCs) that had been pretreated with pioglitazone and/or rosiglitazone on the growth and proliferation rate of MCF-7 cells. The adhesive interaction between the BMSCs and the MCF-7 cancer cells revealed that the pretreatment of BMSCs with a combination of two types of thiazolidinedione drug reduced the growth and proliferation rate of the MCF-7 cells. The proliferation rate of the MCF-7 cells could also be reduced by the non-adhesive interaction of the cancer cells with BMSCs pretreated with pioglitazone and/or rosiglitazone. The growth and proliferation rate reduction effects on the MCF-7 cells may be attributed to the reduction in the protein level of fibroblast growth factor 4 (FGF4) in the conditioned medium of the pretreated BMSCs. The evidence that the low protein level of FGF4 in the conditioned medium of the pretreated BMSCs perturbed the proliferation rate of the MCF-7 cells by reducing the levels of Ki-67 and proliferating cell nuclear antigen transcripts in the cancer cells was also demonstrated in the present study using a FGF4-neutralizing antibody. All the above findings demonstrate that future studies on the correlation between FGF4 and pretreated BMSCs would be beneficial.

An overview of mesenchymal stem cells and their potential therapeutic benefits in cancer therapy (Review)

“…Considering that pioglitazone has been reported to possess anticancer effects (200)(201)(202), it may be beneficial to examine the possibility of priming MSCs with pioglitazone for cancer therapy. After all, using MSCs pretreated with pioglitazone as a strategy to improve the overall therapeutic effects, as reported in our study (199), remains rare. Despite the study on cardiomyogenic transdifferentiation and cardiac function (203), as mentioned above, MSCs pretreated with pioglitazone for cancer therapy remain to be characterized.…”

“…Other studies using pioglitazone as the priming agent also found similar results, where pretreated MSCs had greater therapeutic effects on lung regeneration in an emphysema mouse model ( 197 , 198 ). Pioglitazone has been administered indirectly to breast cancer cells via stem-and-cancer cell interaction ( 199 ). Through this process, modified and viable pretreated stem cells are subsequently administered to patients, and pretreated stem cells are allowed to interact with cancer cells in the patients' bodies.…”

Serum Cytokine Analysis in Patients with Hepatocellular Carcinoma

“…Fibroblast growth factor 4 [FGF4] is a member of the FGF superfamily, which is involved in numerous stages of embryonic development and enhances multiple oncogenic activities, including tumor proliferation, invasion/migration, and colony initiation abilities [63,64]. Although there are some reports on the involvement of FGF4 in the processes of cancers, including lung adenocarcinoma, colorectal cancer, breast cancer, and ovarian cancer [65][66][67][68], little is known about the involvement of FGF4 in HCC. In this study, we found, for the first time, that FGF4 was highly expressed in HCC, suggesting a role as a novel serum biomarker for HCC.…”