[The effects of Tumstatin185-191 on lung adenocarcinoma cell lines and the association with protein kinase B and extracellular regulated protein kinase activation].
OBJECTIVE
to investigate the antitumor effects of tumstatin185-191 as a single agent or combination with cisplatin (DDP) on non-small lung cancer (NSCLC) cell lines A549. In addition, the changes of the protein kinase B(Akt) and extracellular regulated protein kinase (ERK) in cultured NSCLC cells treated by tumstatin185-191 and cisplatin were evaluated.


METHODS
A549 cells were treated with tumstatin185-191 and cisplatin. Cell viability was assessed using the modified 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cell apoptosis was measured by flow cytometry. The activation of Akt and Erk were evaluated by Western blotting.


RESULTS
Tumstatin185-191 inhibited the proliferation of A549 and the IC(50) values of tumstatin 185-191 was 73.7 micromol/L. After cotreatment with 20 micromol/L tumstatin185-191, IC(50) values of cisplatin in A549 cells reduced from 5.2 micromol/L to 3.5 micromol/L, while 40 micromol/L tumstatin185-191 reduced from 5.2 micromol/L to 1.4 micromol/L. The early apoptosis rate was (19.34 +/- 0.97)% in the cotreatment group, (12.5 +/- 2.1)% in cisplatin group and (9.6 +/- 1.6)% in tumstatin185-191 group (F = 5.74, P < 0.01). The levels of phospho-Akt (p-Akt) and phospho-ERK (p-ERK) in the A549 cells were remarkably lower after being treated with tumstatin 185-191, while tumstatin 185-191 treatment whether alone, or in combination with cisplatin, had the similar effects on the protein levels of p-Akt and p-ERK in A549 cells.


CONCLUSIONS
our data suggest that tumstatin185-191 might enhance the sensitivity of A549 cells to cisplatin. The effects of promoting apoptosis and downregulation of proliferation induced by tumstatin185-191 may be mediated through inactivation of the Akt and ERK pathways.
Wang
Wei
W
Department of Respiratory Medicine, the Second Xiangya Hospital, Central South University, Changsha 410011, China.
Chen
Ping
P
Li
Jun-Li
JL
Pei
Yan-Fang
YF
Shuang
Qing-Cui
QC
Liu
Cai-Hong
CH
Cai
Shan
S
Liu
Shao-Kun
SK
Zhu
Lan-Yan
LY
Zhou
Rui
R
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D017209:Apoptosis; D001324:Autoantigens / Q000008:administration & dosage / Q000494:pharmacology*; D045744:Cell Line, Tumor / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage / Q000494:pharmacology; D024141:Collagen Type IV / Q000008:administration & dosage / Q000494:pharmacology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*
D001324:Autoantigens; D024141:Collagen Type IV; C057112:type IV collagen alpha3 chain; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D002945:Cisplatin