[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. CONCLUSION: 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.

[Tumstatin185-191 increases the sensitivity to cisplatin in a cisplatin-resistant human lung adenocarcinoma cell line].

OBJECTIVE: To investigate the effects and related mechanisms of Tumstatin 185-191 as a single agent or in combination with cisplatin on proliferation and apoptosis in a cisplatin-resistant human lung adenocarcinoma cell line A549-DDP cells. METHODS: A549-DDP cells were treated with Tumstatin185-191 and cisplatin at varying concentrations. Cell viability was assessed by a modified 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. 50% inhibiting concentration (IC(50)) values of the chemotherapeutic drugs were analyzed by MTT assay. Cell apoptosis was measured by flow cytometry. The activation of Akt and ERK was evaluated by Western blotting. RESULTS: Tumstatin185-191 inhibited the proliferation of A549-DDP cells and its IC(50) value was 80.25 micromol/L. After cotreatment with 20 micromol/L Tum185-191, the IC(50) value of cisplatin in A549-DDP cells reduced from 77.16 micromol/L to 57.97 micromol/L, the reverse index was 1.33, while with 40 micromol/L Tumstatin185-191 the IC(50) was reduced from 77.16 to 26.40 micromol/L and the reverse index was 2.92. The early apoptosis rate was 19.5% +/- 1.1% in the cotreatment group, while 13.3% +/- 1.5% in cisplatin group and 10.2% +/- 2.0% in Tum185-191 group (F = 4.09, P < 0.05). The levels of phospho-Akt (p-Akt) and phospho-ERK (p-ERK) in the A549-DDP cells were remarkably lower after treatment with Tumstatin 185-191. The Tumstatin 185-191 treatment alone or in combination with cisplatin had a similar effect on the protein levels of p-Akt and p-ERK in A549-DDP cells. CONCLUSION: Our data suggest that Tumstatin185-191 may promote apoptosis, downregulate proliferation and partly reverse the drug resistance of A549-DDP cells to cisplatin. The effects induced by Tum185-191 may be mediated through inactivation of the Akt and ERK pathways.