Niu et al. Journal of Experimental & Clinical Cancer Research 2011, 30:28 http://www.jeccr.com/content/30/1/28 R E S E A R C H Open Access Rapamycin potentiates cytotoxicity by docetaxel possibly through downregulation of Survivin in lung cancer cells Huiyan Niu, Jiahe Wang, Hui Li, Ping He* Abstract Background: To elucidate whether rapamycin, the inhibitor of mTOR (mammalian target of rapamycin), can potentiate the cytotoxic effect of docetaxel in lung cancer cells and to probe the mechanism underlying such enhancement. Methods: Lung cancer cells were treated with docetaxel and rapamycin. The effect on the proliferation of lung cancer cells was evaluated using the MTT method, and cell apoptosis was measured by flow cytometry. Protein expression and level of phosphorylation were assayed using Western Blot method. Results: Co-treatment of rapamycin and docetaxel was found to favorably enhance the cytotoxic effect of docetaxel in four lung cancer cell lines. This tumoricidal boost is associated with a reduction in the expression and phosphorylation levels of Survivin and ERK1/2, respectively. Conclusion: The combined application of mTOR inhibitor and docetaxel led to a greater degree of cancer cell killing than that by either compound used alone. Therefore, this combination warrants further investigation in its suitability of serving as a novel therapeutic scheme for treating advanced and recurrent lung cancer patients. Background Despite recent advancement in the multidisciplinary treatment of cancer, the prognosis for lung cancer remains poor in more advanced stages and recurrent cases. According to World Health Organization, lung cancer ranks at the top in cancer-related mortalities in humans, killing more than one million people each year. Mammalian target of rapamycin (mTOR), a serine/ threonine protein kinase of 289 kDa, is critically involved in cellular signal transduction mediated by phosphatidylinositol 3 kinase (PI3K) [1]. The activation of mTOR results in changes in multiple cellular pro- cesses, e.g., catabolism, anabolism, proliferation, growth and apoptosis [2,3]. Although mTOR is expressed in vir- tually all mammalian cells, it is believed to play a parti- cularly important role in cancer cells [4-7]. Recent reports have suggested that PI3K/Akt/mTOR pathway is often activated in various forms of lung cancer and that * Correspondence: hep@sj-hospital.org Department of Geriatrics, Shengjing Hospital, China Medical University, Shenyang 110004, China this pathway is considered to be important for cancer cells’ survival, proliferation, angiogenesis and resistance to chemotherapy. This pathway can, therefore, be regarded as an attractive target of molecular targeting therapy [8]. Docetaxel (DTX) is one of the most effective che- motherapeutic agents used in the treatment of advanced non-small cell lung cancer (NSCLC). Its anticancer effect is believed to be associated with its ability to induce the polymerization of tubulin, which in turn leads to mitotic arrest. In clinical applications involving lung cancer patients, docetaxel could be either taken together with a platinum compound such as cistaplatin for the first-line treatment or used alone in the second- line treatment of advance stages of NSCLC [9-11]. How- ever, it appears that cancer cells can adapt to become resistant to docetaxel. This currently poses a major clin- ical problem, because it reduces markedly the effective- ness of docetaxel in the treatment of cancers. Docetaxel has also been the standard of care for other solid tumors such as breast, head and neck, ovarian and prostate cancers, etc. It was reported that the activation © 2011 Niu et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.