Niu et al. Journal of Experimental & Clinical Cancer Research 2011, 30:28 http://www.jeccr.com/content/30/1/28 Page 6 of 8 breast cancer, colorectal and gastric carcinomas, neuro- blastoma and NSCLC. All these findings on Survivin indicate that it could be an attractive cancer target. In this study, we were intrigued to find that co-treatment with rapamycin and docetaxel significantly down-regu- lates the expression of Survivin, as shown in Figure 4. Although the underlying mechanism for this down-regu- lation is currently unclear, our finding is consistent with a previous report that found rapamycin reduced IGF- induced Survivin expression in prostate cancer cells [47]. Similarly, Vaira et al. also reported that treatment of rapamycin with taxol at suboptimal concentration resulted in a bigger reduction in Survivin expression than that by either treatment alone [47]. It is possible that when co-treatment of rapamycin and docetaxel synergistically reduced Survivin level beyond the thresh- old for its antiapoptotic activity in cancer cells, the cyto- toxic effect of docetaxel becomes more effective in cancer treatment. In addition, our result suggests that Survivin is essentially involved in lung cancer mainte- nance and progression rather than initiation, which is in agreement with the prevailing hypothesis. Finally, because Survivin is selectively expressed at the G2/M phase of the cell cycle and is a known mitotic regulator of microtubule assembly, the target of action by doce- taxel, it is tempting to speculate an antagonistic inter- play between Survivin and docetaxel [48,49]. Interestingly, recent studies are converging on the notion that inhibition of Survivin in conjunction with docetaxel treatment delivers better cancer-killing effect by reversing the resistance to docetaxel in cancer [50,51]. Activation of the MEK/ERK axis is often associated with cell proliferation and survival [52,53]. Similar to Survivin’s role in cancer, the phosphorylation level of ERK1/2 is often found upregulated in cancer cells and inhibitors against MEK are currently in Phase II clinical trials. In our study, we found that while monotherapies with either rapamycin or docetaxel did not significantly affect the phosphorylation level of ERK1/2, the combi- nation of the two led to a considerable reduction in the amount of phosphorylated ERK1/2(Figure 5). This is sig- nificant, because ERK1/2 activation was known to coun- teract the cancer-killing activity of docetaxel in some malignancies such as leukemia and melanoma [54-56]. It follows that if ERK1/2 activation is blocked due to the combined effects of rapamycin and docetaxel-induced events, cancer cells may be more sensitized to proapop- totic chemotherapeutics. Conclusion In conclusion, the present study demonstrates that mTOR inhibition by rapamycin suppresses lung cancer cell growth and sensitizes tumor cells to docetaxel-induced cytotoxicity. The rapamycin-dependent enhancement of cancer-killing effects by docetaxel is associated with down- regulation of Survivin expression. Although the precise mechanism of interactions between rapamycin and doce- taxel is not presently clear, their proliferation inhibitory and apoptosis-inducing effects may be exerted through down-regulating Survivin expression, either directly or indirectly. Our results suggest that a therapeutic strategy combining specific inhibitor of mTOR with cytotoxic agents may be a promising approach to an improved treat- ment of advanced lung cancer. Acknowledgements This work was supported by a grant from the Natural Science Funds of Liaoning Province (No.20082104) and a grant from the Science and Technology Plan Projects of Liaoning Province (No. 2009225008-10). Authors’ contributions HYN participated in research design, the writing of the paper, the performance of the research and data analysis. JHW participated in the performance of the research and data analysis. HL participated in the performance of the research. PH participated in research design and data analysis. All authors read and approved the final manuscript. Competing interests The authors declare that they have no competing interests. Received: 18 January 2011 Accepted: 10 March 2011 Published: 10 March 2011 References 1. Hay N: The Akt-mTOR tango and its relevance to cancer. Cancer Cell 2005, 8:179-183. 2. Bjornsti MA, Houghton PJ: The TOR pathway: A target for cancer therapy. Nature Reviews Cancer 2004, 4:335-348. 3. Vignot S, Faivre S, Aguirre D, Raymond E: MTOR-targeted therapy of cancer with rapamycin derivatives. Annals of Oncology 2005, 16:525-537. 4. Sparks CA, Guertin DA: Targeting mTOR: prospects for mTOR complex 2 inhibitors in cancer therapy. 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