~ 10% reduction at 12 5 nM Finally, the inhibitory effect and it

~ 10% reduction at 12.5 nM. Finally, the inhibitory effect and its saturating trend towards higher doses of click here rapamycin are the same

for all four cancer cell lines, suggesting rapamycin may act on some targets/pathways common in all of them. Figure 1 Rapamycin exerts growth inhibitory Selleckchem Staurosporine effects in four lung cancer cell lines in a dose-dependent fashion. Cells were treated with increasing levels of rapamycin for 24 hours before cell viability was examined by MTT assay. Control group received treatment of DMSO solution of the same volume and concentration used to dissolve rapamycin. Growth inhibitory effect of rapamycin with docetaxel on lung cancer cells Next we checked the effect of rapamycin on docetaxel-induced growth inhibition in lung cancer cells. It was found that 20 nM rapamycin can potentiate the growth inhibition activity of docetaxel in all four cancer cell lines (Figure 2). This enhancing effect of rapamycin is especially pronounced at low docetaxel concentration (1 nM), having led to an additional 20 – 40% of reduction in cell growth. Although rapamycin does not change the maximum level of cell selleck chemicals growth inhibition elicited by docetaxel (e.g., at 100 nM), the co-treatment of rapamycin with docetaxel effectively lowered the EC50 (concentration needed to achieve 50% of maximal effect) of the latter. Figure 2 Rapamycin administered at 20 nM was able to potentiate the growth inhibitory effect of docetaxel in four lung cancer

cells. Rapamycin induces apoptosis in synergy with docetaxel To further investigate whether the enhancing effect that rapamycin showed in docetaxel-co-treated cancer cells is

associated with an increased level of apoptosis, we performed flow cytomety analysis using Annexin V/propidium iodide-stained cells. As shown in Figure 3, rapamycin enhances the effects of docetaxel in promoting cancer cell death. Discounting the basal apoptosis level as shown in the control sample, the level of apoptosis in the Rapa+DTX group is close to the sum of those in the two monotreaments using either compound alone. These findings indicate that rapamycin may further enhance the efficacy of docetaxel by inducing a higher degree of apoptosis. Figure 3 Rapamycin enhances the apoptosis effect of docetaxel in lung cancer cells. *P < 0.05, next significantly different from untreated control; **P < 0.05, significantly different from either rapamycin or docetaxel monotherapy. Combination treatment of rapamycin with docetaxel decreases the expression of Survivin As we wondered whether the enhancing effect of rapamycin might come from its ability to block cellular pathways that can counteract the cytotoxic activity of docetaxel, the effect of rapamycin on the expression of Survivin was next examined. Treatment of 95D cells with either rapamycin or docetaxel alone resulted in moderate but significant reduction on the level of Survivin expression compared with that of the untreated cells.

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