Abstract: ObjectiveTo investigate the inhibitory effect of artemether (ARE), one of artemisinin derivatives, on the growth and invasion of Lewis lung cancer cells (LCCs) in vitro and explore the possible mechanism. MethodsEffects of ARE on proliferation of LLCs were evaluated by MTT. The invasiveness was detected by Transwell invasion assay, including control, ARE, GW9662 ［the specific inhibitor of peroxisome proliferatoractivated receptor γ (PPARγ)］ and GW9662+ARE group. The expression levels of PPARγ, NFκB p65, Caspase3 mRNA and protein in abovementioned four groups were analyzed by RTPCR and Western blotting, respectively. ResultsARE could inhibit the proliferation of LLCs in time and dosedependent manner, the IC50 value of which in 24, 48, and 72 h were 271.29, 189.08, 65.99 μg/ml, respectively. The fluorescent value of ARE group was 1 744.67, and that of control group was 6 887.00, 4 597.00 of GW+ARE group, as well as 10 012.67 of GW9662 group. It manifested the invasiveness of ARE group was the weakest, which declined significantly compared with control group (t=12.411，P=0.000). The relative quantitative expressions of PPARγ mRNA in ARE and GW9662 group were 2.276±0.534 and 0.362±0.026, respectively. Compared with control group, PPARγ mRNA level in both of ARE and GW9662 group reached statistical significance (t=4.785, P=0.001; t=2.395, P=0.044). PPARγ protein expression in ARE group，GW9662+ARE group and control group were 27 688.33±3 593.06, 21 816.00±1 644.07, 17 716.33±2 273.95, respectively, which was higher in ARE group than that in control and GW+ARE group (t=5.159, P=0.001; t=3.038, P=0.016). NFκB p65 mRNA expression in GW9662+ARE group was 0.346±0.149, which in ARE group and GW9662 group were 0.392±0.187 and 1.720±0.338, respectively. The differences of NFκB p65 mRNA expression level between ARE, and control or GW9662 group were statistically significant (t=3.592, P=0.007; t=7.851, P=0.000). While, the differences of Caspase3 mRNA and protein expression levels among the four groups were not statistically significant (F=1.181, P=0.376; F=0.647, P＞0.05). ConclusionARE may restrain NFκB through upregulating PPARγ to inhibit the proliferation and invasive potential of LLC in vitro, which suggests that PPARγ may be a novel therapeutic target for lung cancer.

Key words: Artemisinins, Lung neoplasms, Peroxisome proliferators activated receptors, Receptor activator of nuclear factor-kappa B