Abstract:
Mesenchymal stem cells (MSCs) have surfaced as ideal candidates for treatment of different therapeutically challenging diseases however their effect on cancer cells is not well determined. In this study, we investigated the effect of MSCs derived from human bone marrow (BM), adipose tissue (AT), and umbilical cord derived MSCs (UC-MSCs) on ovarian cancer.Measurements of ovarian tumor marker proteins were computed by ELISA. Proliferative, apoptosis and anti-inflammatory effects of the MSCs were measured by Flow cytometry (FCM). MMPs expression was measured by RT-PCR.The co-culture of cancer cell lines OVCAR3, CAOV3, IGROV3 and SKOV3 with the conditioned media of MSCs (CM-MSC) and MSCs showed an increase in cellular apoptosis, along with a reduction in the level of CA-125 and a decline of LDH and beta-hCG. A decrease in CD24 of the cancer cell lines in co-culture with the CM-MSCs showed a reduction of the cancer tumorigenicity. In addition, the invasion and aggressiveness of cancer cell lines was significantly decreased by CM-MSC; this was translated by a decrease in MMP-2, MMP-9, and CA-125 mRNA expression, and an increase in TIMP 1, 2, and 3 mRNA expression. An increase in IL-4 and IL-10 cytokines, and a decrease in GM-CSF, IL-6, and IL-9, were also noted.In conclusion, mesenchymal stem cells derived from different sources and their conditioned media appear to have a major role in inhibition of cancer aggressiveness and might be considered as a potential therapeutic tool in ovarian cancer.
摘要:
间充质干细胞(MSC)已经成为治疗不同治疗挑战性疾病的理想候选者,但它们对癌细胞的影响尚未确定。在这项研究中,我们研究了来自人骨髓(BM)的MSCs的作用,脂肪组织(AT),和脐带来源的MSCs(UC-MSCs)对卵巢癌的影响。通过ELISA计算卵巢肿瘤标志物蛋白的测量。增殖,通过流式细胞术(FCM)测量MSCs的凋亡和抗炎作用。通过RT-PCR测量MMP表达。癌细胞系OVCAR3,CAOV3,IGROV3和SKOV3与MSC(CM-MSC)和MSC的条件培养基共培养显示细胞凋亡增加,随着CA-125水平的降低以及LDH和β-hCG的下降。与CM-MSC共培养的癌细胞系的CD24减少显示癌症致瘤性降低。此外,CM-MSC显着降低了癌细胞系的侵袭性和侵袭性;这通过MMP-2,MMP-9和CA-125mRNA表达的降低来翻译,以及TIMP1、2和3mRNA表达的增加。IL-4和IL-10细胞因子的增加,和GM-CSF的减少,还注意到IL-6和IL-9。总之,来自不同来源的间充质干细胞及其条件培养基似乎在抑制癌症侵袭性方面具有重要作用,并且可能被认为是卵巢癌的潜在治疗工具。