Down-regulation of Notch-1 increases co-cultured Jurkat cell sensitivity to chemotherapy.
The bone marrow (BM) microenvironment plays a critical role in malignant cell growth, patient survival and response to chemotherapy in hematologic malignancies. However, the molecular mechanisms of BM stromal cells (BMSCs)-mediated survival of tumor cell remain unclear. In this study, to further evaluate the role of Notch-1 in vivo microenvironment, we investigated the influence of inhibiting Notch-1 pathway by Notch-1 siRNA on Jurkat cells in the co-culture system. We found that Notch-1 signaling in Jurkat cells was further activated by interaction with BMSCs, which inhibited drug-induced apoptosis in Jurkat cells. Notch-1 siRNA down-regulated Notch-1 and restored drug-induced apoptosis in co-cultured Jurkat cells. The possible mechanism of restoration of sensitivity to chemotherapy could be associated with repressed Akt signaling. The results indicated that Notch-1 may be a potential mechanism of BMSCs involvement in the protection of hematopoietic malignant cells from drug-induced apoptosis.
Guo
Dongmei
D
Department of Hematology, Qilu Hospital, Shandong University, Jinan, Shandong, People's Republic of China.
Ye
Jingjing
J
Li
Lizhen
L
Dai
Jianjian
J
Ma
Daoxin
D
Ji
Chunyan
C
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001854:Bone Marrow Cells / Q000378:metabolism; D002450:Cell Communication; D018920:Coculture Techniques; D015536:Down-Regulation / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D019169:Jurkat Cells; D015458:Leukemia, T-Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D051881:Receptor, Notch1 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D017154:Stromal Cells / Q000378:metabolism; D013379:Substrate Specificity; D015854:Up-Regulation
D000970:Antineoplastic Agents; C497761:NOTCH1 protein, human; D034741:RNA, Small Interfering; D051881:Receptor, Notch1; D051057:Proto-Oncogene Proteins c-akt