The Molecular Mechanism Of Curcumin Induced Anoikis In Lung Cancer Cells

Curcumin is hydroxybenzene pigment extract and purify from rhizome of curcuma , the major pharmaceutical effect including anti-inflammation, antioxidant, anti atherosclerosis, anti tumor , anti HIV virus, and another benefit is the toxicity of curcumin is very low. The anti tumor features of curcumin is becoming hot research target for its high efficiency and low toxicity and multi-target, National cancer research center of American already select the curcumin as third generation tumor preventive drug. Although curcumin can suppress the growth of many kinds of tumor cell, and induce the apoptosis of different tumor cell, but until now the detailed molecular mechanism of its anti tumor effect is still unclear. The recent research results suggest that curcumin take effect on multi point of apoptosis process, the sensitivity and pattern of reaction of different tumor cell to curcumin is different, the signal transduction pathway and patterns of signal transduction network reaction induced bycurcumin is different in different tumor cell, so to look for curcumin target signal molecule in different tumor cell is important not only for clinical selective drug in antitumor therapy and also for combine drug therapy for specific target, and this is also important for improve antitumor drug efficiency and reduce cell toxicity of antitumor drug.The apotosis of solid tumor cell without metastasis and normal epithelial cell loss of contact with the extracellular matrix is called anoikis, the features of anoikis is to prevent the fall off cell from planting in other inappropriate place. But those easy metastasis tumor cell can transplant to other place and growth without anoikis happened even after they fall off from solid body of tumor, these phenomena is thought to be the reason of tumor metastasis. So anoikis provide a good research model for signal transduction mechanism about cell growth , death and metastasis. So clarify the mechanism of anoikis signal transduction will provide a new aspect for antitumor metastasis therapy.Lung cancer is the first high incidence tumor in Europe and America with malignance and metastasis feature, so most of research focus on the metastatic mechanism, until now, there is no research reported about whether curcumine can induce lung cancer cell anoikis or not. Based on selected lung cancer cell line with anoikis feature, we use western-blot and other method observe the effect of curcumine on anti-anioikis lung cancer cell and the signal molecules related to cell growth and apoptosis, then we further analysed whether curcumine induced lung cancer cell anoikis depend on the PTEN network or not by gene transfection method.Our experiment take lung cancer cell Calu-3, Spc-Al, A549, PLA801 asresearch subject, we observed the lung cancer cell anti-anoikis features, based on these, we study the curcumin' s effects on lung cancer cell growth circle, anti anoikis and phosphorization of related molecule, we also study the signal transduction molecule and transduction pathway in the lung cancer cell anoikis induced by curcumin.In order to explore the cancer suppression gene PTEN' s effect on anti anoikis of lung caner cell, we use Lipofectamine 2000 technique, observe the effect of PTEN at high and low expression on growth state of anti anoikis lung cancer cell, to clarify that whether or not curcumin induced lung cancer cell apoptosis depend on PTEN pathway. Because of the complexity of cancer cell growth and develop, until now, there is no effective anti tumor drug that can both suppress or kill tumor cell and inhibit metastasis at same time. Our results showed the curcumin can efficiently suppress lung cancer cell growth, induced anoikis of lung cancer cell, suggested that curcumin with the ability to inhibit metastasis.Our experiment major founding:1.We screen out three anti-anoikis lung cancer cells: SPC-AK A549n PLA80K Calu-3 cancer cell aniokis.2. Curcumin take effect on A549 cell, inhibit growth circle at G2 stage.3. Curcumin can effectively suppress four lung cancer line, the suppress -ion depend on curcumin concentration.4. Curcumin can induce anoikis in lung cancer cell Spc~Al> A549, PLA801. 5.The molecule mechanism of curcumin induced anoikis(1) The possible way that curcumin induce lung cancer cell anoikis is to suppress the activity of protein tyrosine kinase, some intra cell protein...