Inhibition of survival pathway could sensitize the tumor cells to chemotherapy
- VernacularTitle:抑制生存传导路径可增加肿瘤细胞化疗敏感性
- Author:
Shen FU
;
Qin ZHANG
;
Yuhui SHAO
- Publication Type:Journal Article
- Keywords:
Akt;
phosphatidylinositol 3-kinase;
adriamycin;
camptothecin
- From:China Oncology
2001;0(02):-
- CountryChina
- Language:Chinese
-
Abstract:
Purpose:To study whether the inhibition of phosphatidylinositol 3-kinase (PI3K)/Akt survival pathway could sensitize the response of tumor cells to some chemotherapyeutic agents. Methods:The different tumor cells has been treated with the combination of isoform specific Akt inhibitor and either adriamycin or camptothecin; the quantitation of the induction of apoptosis by drugs has been estimated with caspase 3 assay; immunoprecipitation western blotting has been used to evaluate the inhibition of the phosphorylation of different isoforms of Akt after the treatment. Results:①The inhibitors could reduce the phosphorylation of Threonine 308 and Serine 473 of isoform specific Akt. ②The inhibition of any one isoform specific Akt could not reverse the resistance of tumor cells tested to chemotherapeutic drugs, but it is not the same case if blocking of two isoforms of both Akt1 and Akt2 was done at the same time. ③The synergistic effects of Akt inhibitors is maybe relative to the level of endogenous PTEN(phosphatase and tensin homolog deleted on chromosome 10) expression. Conclusions:It is required to inhibit two isoforms of both Akt1 and Akt2 in order to maximally sensitize the tumor cells to chemotherapy.
