[To inhibit ERK for enhancing chemotherapy sensitivity of drug-resistance cell lines of leukemia and ovarian carcinoma].
The aim was to study the roles of extracellular regulated protein kinases (ERK) and telomerase activity in drug resistance of human leukemia and ovarian carcinoma cells. Flow cytometry was used to analyze apoptosis rate. Telomere repeat amplification protocol (TRAP) and bioluminescence analysis method were used for detection of telomerase activity. The phosphorylated ERK(1/2) protein expression was observed by Western blot method. The results showed that the specific inhibitor PD98059 of ERK kinase 1 (MEK(1)) enhanced the sensitivity of HL-60/E6 leukemia cell lines to harringtonine (HRT) or COC1/DDP ovarian carcinoma cell lines to cis-dichlorodiamine platinum (DDP). Both PD98059 and chemotherapy drugs HRT and DDP reduced the phosphorylated ERK(1) and ERK(2) protein expression level, and down-regulated the telomerase activity. The sole action of each was inferior to the combination action of PD98059 and HRT or DDP. In conclusion, ERK and telomerase serve a function to some extent in drug resistance of leukemia and ovarian carcinoma cells. The inhibition of ERK signal transduction pathways led to reduction of phosphorylated ERK(1) and ERK(2) protein expression level, and successionally down-regulated the telomerase activity. The final result was to enhance the sensitivity of HL-60/E6 to HRT or COC1/DDP to DDP.
Li
Deng-Ju
DJ
Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Zhang
Yao-Zhen
YZ
Huang
Wei
W
Meng
Fan-Kai
FK
D017209:Apoptosis / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D005419:Flavonoids / Q000494:pharmacology*; D018922:HL-60 Cells; D006801:Humans; D007938:Leukemia / Q000188:drug therapy* / Q000473:pathology; D020928:Mitogen-Activated Protein Kinases / Q000032:analysis / Q000037:antagonists & inhibitors*; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D019098:Telomerase / Q000378:metabolism
D004791:Enzyme Inhibitors; D005419:Flavonoids; D020928:Mitogen-Activated Protein Kinases; D019098:Telomerase; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one