Umbilical cord tissue-derived mesenchymal stem cells induce apoptosis in PC-3 prostate cancer cells through activation of JNK and downregulation of PI3K/AKT signaling.
Umbilical cord tissue-derived mesenchymal stem cells induce apoptosis in PC-3 prostate cancer cells through activation of JNK and downregulation of PI3K/AKT signaling.
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DOI：
10.1186/scrt443
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发表时间：
2014-04-16
影响因子：
7.5
通讯作者：
Kim SH
中科院分区：
文献类型：
--
作者：
Han I;Yun M;Kim EO;Kim B;Jung MH;Kim SH
尽管间充质干细胞（mesenchymal stem cells，MSCs）在肝癌和乳腺癌细胞中具有抗肿瘤潜能，但人脐带间充质干细胞（human umbilical cord mesenchymal stem cells，hUCMSCs）在前列腺癌细胞中的抗肿瘤机制尚不清楚。因此，在本研究中，我们阐明了hUCMSCs在PC-3前列腺癌细胞中的体外和体内抗肿瘤活性。从脐带的沃顿胶中分离hUCMSCs，并通过诱导分化、成骨和脂肪形成来表征。在与PC-3前列腺癌细胞共培养的条件下评价UCMSC对肿瘤生长的抗肿瘤作用。将PC-3细胞皮下（sc）注射到裸鼠的左胁腹中，并将UCMSC皮下注射到同一小鼠的右胁腹中。我们发现hUCMSCs在共培养条件下抑制PC-3细胞的增殖。Western blotting结果显示，hUCMSCs诱导PC-3细胞caspase 9/3和PARP的裂解，激活c-jun NH 2-terminal kinase（JNK）和Bax，减弱磷脂酰肌醇3-激酶（PI 3 K）/ AKT和细胞外信号调节激酶（ERK）的磷酸化，抑制Bcl-2、Bcl-xL、Survivin、Mcl-1和cIAP-1等生存基因的表达。相反，我们发现特异性JNK抑制剂SP 600125处理抑制了hUCMSCs诱导的PC-3细胞中caspase 9/3和PARP的裂解。在Nu/nu-BALB/c小鼠中检测到hUCMSC向K562异种移植瘤区域的归巢和TUNEL阳性细胞。这些结果表明，UCMSCs抑制肿瘤生长，并具有抗肿瘤潜力的PC-3前列腺癌治疗。
Although mesenchymal stem cells (MSCs) have antitumor potential in hepatocellular carcinoma and breast cancer cells, the antitumor mechanism of human umbilical cord mesenchymal stem cells (hUCMSCs) in prostate cancer cells still remains unclear. Thus, in the present study, we elucidated the antitumor activity of hUCMSCs in PC-3 prostate cancer cells in vitro and in vivo. hUCMSCs were isolated from Wharton jelly of umbilical cord and characterized via induction of differentiations, osteogenesis, and adipogenesis. Antitumor effects of UCMSCs on tumor growth were evaluated in a co-culture condition with PC-3 prostate cancer cells. PC-3 cells were subcutaneously (sc) injected into the left flank of nude mice, and UCMSCs were sc injected into the right flank of the same mouse. We found that hUCMSCs inhibited the proliferation of PC-3 cells in the co-culture condition. Furthermore, co-culture of hUCMSCs induced the cleavage of caspase 9/3 and PARP, activated c-jun NH2-terminal kinase (JNK), and Bax, and attenuated the phosphorylation of phosphatidylinositol 3-kinase (PI3K)/ AKT, extracellular signal-regulated kinase (ERK), and the expression of survival genes such as Bcl-2, Bcl-xL, Survivin, Mcl-1, and cIAP-1 in PC-3 cells in Western blotting assay. Conversely, we found that treatment of specific JNK inhibitor SP600125 suppressed the cleavages of caspase 9/3 and PARP induced by hUCMSCs in PC-3 cells by Western blotting and immunofluorescence assay. The homing of hUCMSCs to, and TUNEL-positive cells on, the K562 xenograft tumor region were detected in Nu/nu-BALB/c mouse. These results suggest that UCMSCs inhibit tumor growth and have the antitumor potential for PC-3 prostate cancer treatment.
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