Molecular mechanism of cell apoptosis by paclitaxel and pirarubicin in a human osteosarcoma cell line.
BACKGROUND
Paclitaxel and pirarubicin exhibit cytotoxic and antitumor activities. However, little is known about the apoptosis-inducing effects of paclitaxel and pirarubicin on human osteosarcoma MG-63 cells.


METHODS
The effects of paclitaxel and pirarubicin on cell cycle arrest and apoptosis were studied in MG-63 cells using flow cytometry. PCNA, Bcl-2, Bax, cyclin D1 and cyclin E expression was assessed by Western blotting.


RESULTS
Paclitaxel and pirarubicin caused G2/M and G0/G1 cell cycle arrest in MG-63 cells, respectively. Apoptosis of MG-63 cells mediated by paclitaxel was dependent on treatment duration. Interestingly, in cells treated with pirarubicin, apoptosis was related to treatment duration at concentrations of 10(2)-10(3) nM, whereas the effect of treatment duration was less marked at concentrations >10(4)-10(5) nM. Furthermore, paclitaxel and pirarubicin suppressed the expression of PCNA, cyclin D1, cyclin E and Bcl-2, and increased Bax expression.


CONCLUSIONS
These results suggest that the G2/M or G0/G1 cell cycle arrest and apoptosis induced by paclitaxel and pirarubicin are Bcl-2/Bax dependent, suggesting favorable effects of combination therapy with paclitaxel and pirarubicin in the treatment of osteosarcoma.
Liu
Si-Yuan
SY
Department of Orthopedic Oncology, Third Hospital, Hebei Medical University, Shijiazhuang, PR China. LiusiYuan2004 @ yahoo.com
Song
Shu-Xia
SX
Lin
Liang
L
Liu
Xing
X
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage / Q000031:analogs & derivatives; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D012516:Osteosarcoma / Q000188:drug therapy* / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D004317:Doxorubicin; C027260:pirarubicin; D017239:Paclitaxel