[Protein kinase C inhibitor Gö6976 sensitizes arsenic trioxide-induced cell apoptosis in chronic myeloid leukemic cells].
To investigate the As(2)O(3)-chemosensitization of Gö6976 in K562 cells by its abrogation of As(2)O(3)-induced G(2)/M cell cycle arrest, K562 cells were treated with As(2)O(3) (5 micromol/L) and Gö6976 with various concentrations, the distributions of cell cycles were detected by flow cytometry, the cell viability was observed by trypan blue exclusion test and cell proliferation was tested by MTT assay. The results indicated that having treated by As(2)O(3) for 24 h and 48 h, the proportion of K562 cells in G(2)/M phase were (38.02 +/- 7.70)% and (32.58 +/- 7.43)% respectively, and no obvious cell apoptosis appeared. 50 nmol/L Gö6976 combined with As(2)O(3) decrease the proportion of cells in G(2)/M phase to (23.24 +/- 2.93)% and (16.18 +/- 1.60)% respectively and increase the proportion of cells in subG(1) phase to (11.82 +/- 2.31)% and (27.80 +/- 2.89)% respectively. Gö6976 abrogated G(2)/M cell cycle arrest induced by As(2)O(3) and increased cell apoptosis in a concentration- and time-dependent manner. Additionally, comparing to the control group, Gö6976 combined with As(2)O(3) decreased the cell viability and depressed the cell proliferation, but Gö6976 alone showed no same effect on them. In conclusion, the effects of AS(2)O(3)-chemosensitization of Gö6976 on K562 cells is associated with its abrogation of As(2)O(3)-induced G(2)/M cell cycle arrest.
Wu
Xiao-Fei
XF
Department of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. xw909@163.net
Chen
Zhi-Chao
ZC
Liu
Zhong-Ping
ZP
You
Yong
Y
Li
Wei-Ming
WM
Zou
Ping
P
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D002227:Carbazoles / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D020014:K562 Cells; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000473:pathology / Q000503:physiopathology; D010087:Oxides / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D013997:Time Factors
D000970:Antineoplastic Agents; D001152:Arsenicals; D002227:Carbazoles; D004791:Enzyme Inhibitors; D010087:Oxides; C081021:Go 6976; D011493:Protein Kinase C; D000077237:Arsenic Trioxide