Effect of Cx43 gene-modified leukemic bone marrow stromal cells on the regulation of Jurkat cell line in vitro.
We recently reported that Cx43 expression and gap junction intercellular communication (GJIC) between acute leukemic bone marrow stromal cells (BMSCs) were deficient, which could recovery after effective chemotherapy. However, the exact role of GJIC in the hematopoietic microenvironment in leukemic cell death and proliferation is not clear. We show here that following transfection with the Cx43 gene, GJIC function was increased between leukemic BMSCs. Furthermore, compared with leukemic cells alone, the proliferation and apoptosis of leukemic cells co-cultured with BMSCs were inhibited, the percentage of G0-phase cells was higher; and expression of p53 increased and bax decreased. However, after co-culturing leukemic cells with Cx43-modified BMSCs, the number of proliferative and spontaneously apoptotic Jurkat cells increased; the percentage of G0-phase cells decreased; the expression of p53 decreased; and bax increased. Compared with Jurkat cells co-cultured with BMSCs and Jurkat cells alone, the sensitivity of leukemic cells co-cultured with Cx43-modified BMSCs to chemotherapeutics increased. Our data suggests that GJIC between leukemia BMSCs is one of the impact factor to the proliferation, apoptosis and drug sensitivity of co-cultured leukemic cells. Up-regulating its function can inhibit the protective effects of leukemic BMSCS and enhance the efficacy of therapies in hematologic malignancies.
Department of Hematology, Xinqiao Hospital, The Third Military Medical University, Xinqiao Street, Chongqing, China.
Xi
X
Zhang
Yao
Y
Liu
Ying-jian
YJ
Si
Xing-hua
XH
Chen
Zhong-jun
ZJ
Li
Lei
L
Gao
Li
L
Gao
Cheng
C
Zhang
D000328:Adult; D017209:Apoptosis; D015153:Blotting, Western; D001854:Bone Marrow Cells / Q000378:metabolism / Q000473:pathology*; D002450:Cell Communication; D002453:Cell Cycle; D049109:Cell Proliferation; D018920:Coculture Techniques; D018031:Connexin 43 / Q000235:genetics*; D005260:Female; D005434:Flow Cytometry; D017629:Gap Junctions; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology*; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
C494826:BAX protein, human; D018031:Connexin 43; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein