Correlation between survivin mRNA expression and homoharringtonine induced apoptosis of malignant hematopoietic cells.
BACKGROUND
The inhibitor of apoptosis (IAP) gene family is involved in the suppression of apoptotic cell death as well as an increasing number of seemingly unrelated cellular functions. It is not known, however, whether IAP expression in malignant hematopoietic cells is affected by chemotherapeutic agents such as homoharringtonine (HHT). In this study, we investigated mRNA expression levels of IAPs, especially survivin, in various hematopoietic cell lines in relation with apoptosis induced by HHT.


METHODS
Semiquantitative reverse transcriptase polymerase chain reaction was used to determine survivin mRNA levels. Cell apoptosis was examined by flow cytometry. Cell viability and proliferation assay was evaluated by MTT. The experiments were performed on the malignant hematopoietic cell lines MUTZ-1, K562, Jurkat, RMPI and HL60, with or without survivin antisense-oligodeoxynucleotides (AS-ODN) and HHT.


RESULTS
The expression levels of survivin mRNA were variable in the cell lines and negatively correlated to HHT induced cell apoptosis. Survivin AS-ODN significantly decreased mRNA level of survivin, but not those of bax and bcl-2. Survivin also inhibited MUTZ-1 cell growth and induced apoptosis in a dose dependent manner. AS-ODN and HHT showed synergistic effect on MUTZ-1 cell growth.


CONCLUSIONS
The apoptotic effect of HHT on the hematopoietic cell lines is associated with decreased level of survivin expression. Survivin could be a new marker for drug sensitivity and a new target for cancer treatment.
Cai
Zhen
Z
Department of Hematology, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China. caizhen1@yahoo.com
Bao
Han-ying
HY
Lin
Mao-fang
MF
D000754:Anemia, Refractory, with Excess of Blasts / Q000378:metabolism / Q000473:pathology*; D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle; D002460:Cell Line; D006248:Harringtonines / Q000494:pharmacology*; D000077863:Homoharringtonine; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D007938:Leukemia / Q000378:metabolism / Q000473:pathology*; D008869:Microtubule-Associated Proteins / Q000235:genetics*; D009363:Neoplasm Proteins; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D000077022:Survivin; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; C107489:BIRC5 protein, human; D006248:Harringtonines; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D016376:Oligonucleotides, Antisense; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D000077022:Survivin; D051028:bcl-2-Associated X Protein; D000077863:Homoharringtonine