The Effects And Mechanisms Of The Combination TRAIL And Vinorelbine On Lung Cancer Cells

Objective：To investigate the effect of TRAIL combined with vinorelbine on proliferation ofadenocarcinoma of lung A549, and to investigate its possible mechanism.Methods：1．To detect the effect of TRAIL or vinorelbine respectively on proliferation ofadenocarcinoma of lung A549: A549cells were treated with various concentration ofTRAIL or vinorelbine for24~48hours. Proliferation inhibition rate of A549cellswere measured by MTT assay, and half inhibitory concentration (IC50) were analyzed.2．To probe the effect of different groups on inducing apoptosis of adenocarcinomaof lung A549: Divided the lung cancer cells A549into four groups: control, TRAIL,vinorelbine, TRAIL with vinorelbine, every group was treated with associatedconditions and administrations for48hours. Morphology changes of A549cells wereobserved through microscopy. The apoptosis rates of different groups were detectedby flow cytometry.3．To test the expression of apoptosis-related protein in A549cells intervented bydifferent group drugs: every group was treated with associated conditions andadministrations for48hours, Western blot was used to quantify the change of theapoptosis-related protein DR4、DR5、caspase-3.Results：1．TRAIL could induce apoptosis in the lung adenocarcinoma cell line A549,presenting obvious dose-dependent cytotoxicity through MTT, and IC50of24h was254.70μg/ml, while IC50of48h was101.98μg/ml. vinorelbine also could induceapoptosis in the lung adenocarcinoma cell line A549, presenting obviousdose-dependent cytotoxicity through MTT, and IC50of24h was25.12μg/ml, while IC50of48h was8.71μg/ml. The apoptosis rate of the lung adenocarcinoma cell lineA549showed a significant difference to the group of TRAIL(P<0.05). Andsynergistic effect of TRAIL combined with vinorelbine was found, the CDI was1.3104.2．The apoptosis rate of the lung adenocarcinoma cell line A549was obviouslyincreased by intervention of TRAIL combined with vinorelbine (32.6%), compared tothe group of TRAIL(6.4%) or vinorelbine(6.9%)treatment with a significantdifference(P<0.05)according to the flow cytometry.3．The expression level of the apoptosis-related factors DR4, DR5and caspase-3was upregulated in group of TRAIL combined with vinorelbine, and there was asignificant difference between different groups (P<0.05).Conclusions：1．TRAIL combined with vinorelbine can apparently increase the apoptosis rate ofthe lung adenocarcinoma cell line A549;2. The expression level of the apoptosis-related factors DR4, DR5and caspase-3may be involved in the mechanism increased apoptosis.