scholarly journals The Radio-Sensitivity Effects of Human Umbilical Cord Wharton’s Jelly Mesenchymal Stem Cell’s Conditional Medium on MDA-MB-231 Cells

Author(s):  
Hamed Shoghi ◽  
Niloofar Neisi ◽  
Ghasem Saki ◽  
Mohamad Javad Tahmasebi Biragani ◽  
Amir Danyaei

Background: While radiotherapy is the important modality in the treatment of breast cancer cells, radioresistance of some tumor cell lines such as MDA-MB-231 is still a limitation that must be considered. Objectives: The present study was done to examine the effect of the conditioned medium of the human umbilical cord Wharton's jelly stem cells (hWJSCs + CM) on the radiosensitivity of MDA-MB-231 cells in combination with megavoltage-radiations. Methods: Groups are Control, CM, GY, and GY + CM. In irradiation groups, breast cancer cells were exposured with 4, 6, and 8 Gy radiation. Each group includes different doses of the conditioned medium of hWJSCs (25%, 50%, and 75%). Results: The MTT assay showed that the proliferative activity of Gy + CM groups at all doses of condition medium decreased significantly compared with the control, rather than Gy groups. Trypan blue viability test showed that the survival rate of MDA-MB-231 cells significantly reduced in the CM and 8 Gy + CM groups compared with the control group, rather than Gy groups. MDA-MB-231 cells lost their normal spindle shape and became thinner and longer after 48h of treatment and the number of cells sharply reduced in Gy + CM groups compared with the control group, rather than Gy groups. These changes were accompanied by inducing significant up-regulation of Interleukin-6 (IL-6) in the 4 Gy + CM and 8 Gy + CM groups compared with the control group, rather than Gy groups and as a consequence, a decrease in the amount of transmembrane tumor necrosis factor-α (tmTNF-α) as a pro-inflammatory cytokine in the Gy + CM groups compared with the control group, rather than Gy groups. Also, we indicated that the radiosensitivity of breast cancer cells was probably enhanced by an increase in different doses of the conditioned medium of stem cells. Conclusions: Treatment of the MDA-MB-231 cells with hWJSCs + CM plus radiotherapy inhibited the growth and proliferation of cancer cells and this method is a novel strategy for breast cancer therapy by overcoming radioresistance.

Oncotarget ◽  
2016 ◽  
Vol 7 (23) ◽  
pp. 34172-34179 ◽  
Author(s):  
Ching-Ju Shen ◽  
Te-Fu Chan ◽  
Chien-Chung Chen ◽  
Yi-Chiang Hsu ◽  
Cheng-Yu Long ◽  
...  

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ya-Han Liang ◽  
Jiann-Ming Wu ◽  
Jui-Wen Teng ◽  
Eric Hung ◽  
Hwai-Shi Wang

AbstractBreast cancer is the leading cause of cancer-related death for women. In breast cancer treatment, targeted therapy would be more effective and less harmful than radiotherapy or systemic chemotherapy. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been shown to induce apoptosis in cancer cells but not in normal cells. Mesenchymal stem cells have shown great therapeutic potential in cancer therapy owing to their ability of homing to tumor sites and secreting many kinds of anti-tumor proteins including TRAIL. In this study, we found that IL-1β-stimulated human umbilical cord-derived mesenchymal stem cells (hUCMSCs) enhance the expression of membrane-bound and soluble TRAIL. Cellular FADD-like IL-1β-converting enzyme inhibitory protein (cFLIP) is an important regulator in TRAIL-mediated apoptosis and relates to TRAIL resistance in cancer cells. Previous studies have shown that embelin, which is extracted from Embelia ribes, can increase the TRAIL sensitivity of cancer cells by reducing cFLIP expression. Here we have demonstrated that cFLIPL is correlated with TRAIL-resistance and that embelin effectively downregulates cFLIPL in breast cancer cells. Moreover, co-culture of IL-1β-stimulated hUCMSCs with embelin-treated breast cancer cells could effectively induce apoptosis in breast cancer cells. The combined effects of embelin and IL-1β-stimulated hUCMSCs may provide a new therapeutic strategy for breast cancer therapy.


2021 ◽  
Author(s):  
Mahdieh Farhoudi Sefidan Jadid ◽  
Parisa Emami ◽  
Pouya Goleij ◽  
Vahidreza Karamad ◽  
Afshin Khorrami ◽  
...  

Abstract Background and aim: Colorectal cancer (CC) is aggressive cancer and the major cause of death worldwide that need the development of novel and effective therapeutic methods. Recently suggested that the human Wharton’s jelly stem cells (hWJSCs) have an anti-proliferation activity against of several cancer cells through apoptosis induction. Therefore, this study aimed to investigate the effects of conditioned medium and cell lysate of human umbilical cord hWJSCs against the HT-29 cancer cell line and mechanisms of apoptosis induction.Methods: In this study, the hWJSCs conditioned medium and cell lysate were prepared from 10 human umbilical cord samples. The effects of hWJSCs conditioned medium and cell lysate were evaluated on the viability, migration, invasion, and apoptosis of HT-29 CC cell line. The expression of apoptosis related BAX, BCL2, SMAC, SURVIVIN, and Cas9 genes were evaluated in CC cells treated with hWJSCs conditioned medium and cell lysate.Results: We observed that conditioned medium and cell lysate of hWJSCs decrease CC cells viability, proliferation, migration, and invasion in a concentration- and time-dependent manner. Moreover, conditioned medium and cell lysate increased apoptosis rate of CC cells, which can be due to increase BAX, SMAC, and Cas9 genes, as well as decrease BCL2 and SURVIVIN genes.Conclusions: Our study suggest that conditioned medium and cell lysate of hWJSCs can inhibit CC cells through induction of apoptosis. However, further studies on are required to more accurate results.


2019 ◽  
Author(s):  
Xiaoli Lu ◽  
Guangzhi Liu ◽  
Lenan Cheng ◽  
Licong Ge ◽  
ZiYi Zhao ◽  
...  

Abstract Objective:To investigate the effects of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) on apoptosis and proliferation of human ovarian cancer SKOV3 cells and to explore mechanism.Methods:hUC-MSCs were isolated and cultured by tissue block adherent culture method. The hUC-MSCs phenotype were identified by flow cytometry. The hUC-MSCs lysate and conditioned medium,directly combine were used to treat SKOV3 cells.The effects on the proliferation,apoptosis,mechanism of SKOV3 cells were examined by cell counting kit-8(CCK-8),Annexin V-FITC/PI,quantitative real time polymerase chain reaction(RT-qPCR) and spheroid formation assays.Establish ovarian cancer xenograft models,1X 106 hUC-MSCs and 2 X 106 hUC-MSCs were administrated into the mice t rear back tumor tissue. After three injections of hUC-MSCs, the nude mice were sacrificed after 1 week of observation.Remove tumor tissue. Observed tumor volume changes every 3 days after the start of the experiment. The expression of CD34 and VEGF were detected by immunohistochemistry.Results:Human umbilical cord mesenchymal stem cells were cultured and isolated from tissue block. Flow cytometry results revealed that the hUC-MSCs marks CD44 and CD29, but not CD45 and CD34 were expressed on obtained cells. The apoptosis of SKOV3 cells was induced by hUC-MSCs lysate, conditioned medium and Transwell co-culture method in SKOV3 cells, and the apoptosis rate was higher with increasing concentration. hUC-MSCs conditioned medium and Transwell co-culture method can inhibit cell proliferation. After adding experimental factors, the conditioned medium and Transwell co-culture method can down-regulate the transcription of PI3KCA, AKT and BCL-2 genes in SKOV3 cells, and up-regulate the Caspase-3 gene.The tumor volume of the experimental group was smaller than that of the control group during the observation period. The expression levels of CD34 and VEGF in the experimental group were significantly lower than those in the control group(P<0.05).Conclusion: The conditioned medium of hUC-MSCs and the co-culture method of hUC-MSCs and SKOV3 can significantly inhibit the proliferation of SKOV3 cells, which is mainly achieved by inhibiting PI3K/AKT signaling pathway. hUC-MSCs can inhibit the growth of subcutaneous subcutaneous transplantation and the expression of CD34 and VEGF in ovarian cancer. It provides a new idea for the treatment of ovarian cancer.


2021 ◽  
Author(s):  
Reyhaneh Abolghasemi ◽  
Somayeh Ebrahimi-barough ◽  
Jafar Ai

Abstract Background: Tumor growth and metastasis eventuate from an interaction between cancer cells and the surrounding extracellular matrix. Recent studies demonstrated inhibitory effects of mesenchymal stem cells on breast tumors. Likewise, the emerging interest in statins as anticancer agents is based on their pleiotropic effects. In the present study, we investigated whether atorvastatin and umbilical cord matrix derived mesenchymal stem cells-conditioned medium alone and combined with each other affect the MCF7 cancer cells viability and interactions.Methods: We measured the viability, apoptosis, and necrosis of MCF7 by MTT assay, Annexin-V/PI staining by flow cytometry, and quantitative real-time PCR. Two-dimensional culture and hanging drop aggregation assay illustrated the morphological changes in single cancer cells and spheroid configuration respectively. We traced the MCF7 migration via scratch-wound healing and trans-well assays. Results: The results showed inhibition of cancer cell viability in all treated groups compared with the control group, but the effect of atorvastatin and conditioned medium combination was further than each one alone. Cancer cells shrinkage and chromatin condensation in the inverted light microscopy and fluorescent staining microscopy indicated apoptosis in treated cells. The annexin V/PI analysis especially in the combination-treated group displayed decreasing in DNA synthesis and cell cycle arrest. The mRNA expressions of caspases 3, 8, 9, and Bcl-2 genes were along with extrinsic and intrinsic apoptosis pathways. Conditioned medium disrupts the connections between cancer cells in the three-dimensional spheroids configuration. The migration of treated cells across the wound area and trans-well diminished, particularly in the combination-treated group. Conclusions: For the first time, the synergistic anti-proliferative and anti-motility effect of atorvastatin along with human umbilical cord mesenchymal stem cells-derived conditioned medium on MCF7 breast cancer cells have been proved. These findings point to some new therapeutic strategies with a focus on the crosstalk between breast cancer cells and microenvironment.


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