| Content Provider | Springer Nature : BioMed Central |
|---|---|
| Author | Han, Zhipeng Jing, Yingying Xia, Yong Zhang, Shanshan Hou, Jing Meng, Yan Yu, Fenghai Liu, Xiaoqing Wu, Mengchao Zhang, Ping Wei, Lixin |
| Abstract | Background Mesenchymal stem cells (MSCs) have been reported to play an important role in tumor growth. Inflammation is an important feature of hepatocellular carcinoma (HCC). Certain inflammatory cytokines produced in tumor microenvironment modulate functional activities of MSCs. At the present time, however, the role of MSCs in the development of HCC cell resistance to chemotherapy in the inflammatory microenvironment during tumor growth has not yet been identified. Methods MTT and PI/Annexin V-FITC assay were employed to examine the proliferation and apoptosis of HCC cell lines. The expression of TGF-β are detected by Realtime PCR and Western blot. GFP tagged LC3 expression vector and electron microscopy are utilized to demonstrate the occurrence of autophagy. Results We observed that MSCs pretreated with the combination of IFN-γ and TNF-α induced resistance to chemotherapy in HCC cell lines in both the in vitro and in vivo circumstances. Following exposure to conditioned medium of MSCs that were pre-treated with IFN-γ plus TNF-α, HCC cell line cells underwent autophagy which serves as a protective mechanism for HCC cells to resist the cell toxicity of chemotherapeutic agents. Treatment of HCC cell line cells with autophagy inhibitor effectively reversed the MSCs-induced resistance to chemotherapy in these cells. Stimulation with the combination of IFN-γ and TNF-α provoked expression of TGF-β by MSCs. MSCs-induced chemoresistance in HCC cell lines was correlated with the up-regulation of TGF-β expression by MSCs. Knockdown of TGF-β expression by MSCs with siRNA attenuated MSCs-induced chemoresistance in HCC cells. Conclusions These results suggest that increase in TGF-β expression by MSCs in the inflammatory microenvironment of HCC promotes the development of chemoresistance in HCC cells. |
| Related Links | https://cellandbioscience.biomedcentral.com/counter/pdf/10.1186/2045-3701-4-22.pdf |
| Ending Page | 11 |
| Page Count | 11 |
| Starting Page | 1 |
| File Format | HTM / HTML |
| ISSN | 20453701 |
| DOI | 10.1186/2045-3701-4-22 |
| Journal | Cell & Bioscience |
| Issue Number | 1 |
| Volume Number | 4 |
| Language | English |
| Publisher | BioMed Central |
| Publisher Date | 2014-04-28 |
| Access Restriction | Open |
| Subject Keyword | Cell Biology Microbiology Stem Cells Neurobiology Proteomics Mesenchymal stem cells Inflammation Autophagy Hepatocellular carcinoma |
| Content Type | Text |
| Resource Type | Article |
| Subject | Biochemistry, Genetics and Molecular Biology |
| Journal Impact Factor | 6.1/2023 |
| 5-Year Journal Impact Factor | 7/2023 |
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