Effect of human WEE1 and stem cell factor on human CD34+ umbilical cord blood cell damage induced by chemotherapeutic agents.
Myelosuppression is one of the major side-effects of most anticancer drugs. To achieve myeloprotection, one bicistronic vector encoding anti-apoptotic protein human WEE1 (WEE1Hu) and proliferation-stimulating stem cell factor (SCF) was generated. In this study, we selected human umbilical cord blood CD34+ cells as the in vitro model in an attempt to investigate whether WEE1Hu, rather than conventional drug-resistant genes, can be introduced to rescue cells from the damage by chemotherapeutic agents such as cisplatin, adriamycin, mitomycin-c and 5-fluorouracil. Cell viability and cytotoxicity assay, colony-forming units in culture assay and externalization of phospholipid phosphatidylserine analysis showed that the expression of WEE1Hu and SCF in CD34+ cells provided the cells with some protection. These findings suggest that the expression of WEE1Hu and SCF might rescue CD34+ cells from chemotherapy-induced myelosuppression.
Laboratory of Molecular and Immuno-Pharmacology, Department of Immunology and Pharmacology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Ping
P
LEI
Yong
Y
HE
Wenfang
W
SHI
Jilin
J
PENG
Sha
S
WU
Huifen
H
ZHU
Jianguo
J
CHEN
Guanxin
G
SHEN
D018952:Antigens, CD34 / Q000097:blood*; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology / Q000627:therapeutic use; D003114:Colony-Forming Units Assay; D004317:Doxorubicin / Q000494:pharmacology / Q000627:therapeutic use; D005312:Fetal Blood / Q000187:drug effects*; D005472:Fluorouracil / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D016685:Mitomycin / Q000494:pharmacology / Q000627:therapeutic use; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D010957:Plasmids; D011505:Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D019089:Stem Cell Factor / Q000235:genetics* / Q000378:metabolism; D014162:Transfection
D018952:Antigens, CD34; D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; D019089:Stem Cell Factor; D016685:Mitomycin; D004317:Doxorubicin; D007770:L-Lactate Dehydrogenase; D011505:Protein-Tyrosine Kinases; C499349:WEE1 protein, human; D002945:Cisplatin; D005472:Fluorouracil