Blockage of mTOR signaling pathway by rapamycin contributes to inhibition of tumor cell proliferation in ALK-positive lymphoid cell strains.
- Author:
Ling GU
1
;
Jin-Fan LI
;
Ju GAO
;
Yi-Ping ZHU
;
Qiang LI
;
Cang-Song JIA
;
Cheng-Yan ZHOU
;
Zhi-Gui MA
Author Information
- Publication Type:Journal Article
- MeSH: Animals; Apoptosis; drug effects; Cell Cycle; drug effects; Cell Line, Tumor; Cell Proliferation; drug effects; Humans; Intracellular Signaling Peptides and Proteins; metabolism; Lymphoma; metabolism; pathology; Mice; Protein-Serine-Threonine Kinases; metabolism; Protein-Tyrosine Kinases; metabolism; Receptor Protein-Tyrosine Kinases; Ribosomal Protein S6 Kinases, 70-kDa; metabolism; Signal Transduction; drug effects; Sirolimus; pharmacology; TOR Serine-Threonine Kinases
- From: Chinese Journal of Hematology 2008;29(10):662-666
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo investigate the relationship between mTOR signaling pathway and ALK-positive lymphoid cell lines.
METHODSThe expression of the downstream effector proteins of mTOR were analyzed by Western blot before and after Karpas299, BaF3/NPM-ALK and BaF3 cell lines treated with rapamycin. Effect of rapamycin on cell proliferation was detected by MTT assay. FACS was used to analyze apoptosis and cell cycles.
RESULTSmTOR signaling phosphoproteins, p-p70S6K and p-4E-BP1 were highly expressed in ALK(+) Karpas299, BaF3/NPM-ALK and parental BaF3 cell lines, and they were dephosphorylated after 1 h withdrawal of IL-3 in BaF3 cells. After 48 h exposure to 10 nmol/L rapamycin, p-p70S6K and p-4E-BP1 proteins expression were decreased, and mainly for the former. The relative inhibitory rate to its control cells was 24.4% in Karpas299, 37.8% in BaF3/NPM-ALK and 61.6% in BaF3. The apoptotic ratio was increased from (11.97 +/- 0.11)% to (15.87 +/- 0.62)% in Karpas299 (P < 0.05), from (3.23 +/- 0.11)% to (7.67 +/- 0.49)% in BaF3 (P < 0.05) and from (1.90 +/- 0.47)% to (2.80 +/- 0.27)% in BaF3/NPM-ALK (P > 0.05). The fraction of G(1) phase cells increased from (37.63 +/- 1.91)% to (69.77 +/- 5.44)% in BaF3/NPM-ALK, from (31.13 +/- 2.51)% to (40.70 +/- 1.47)% in Karpas299 and (53.57 +/- 2.22)% to (63.70 +/- 1.20)% in BaF3 (P < 0.05).
CONCLUSIONNPM-ALK kinase can activate mTOR signaling pathway. Rapamycin can inhibit the proliferation of ALK(+) lymphoid cells by blocking mTOR signaling pathway and inducing cell cycling arrest at G(1) phase.
