Patent Abstract:
the present invention relates to a method for treating gefitinib - resistant non - small - cell lung cancer comprising administering an effective amount of a resveratrol analogue , 3 , 4 , 5 , 4 ′- tetramethoxystilbene , to a subject in need thereof . the present invention also relates to a method for inducing apoptosis in gefitinib - resistant nsclc cells comprising contacting the resveratrol analogue to the cells at an effective amount . the present methods are mediated by different signaling pathways connected to cell proliferation and differentiation such as mtor , jnk , and certain egfr phosphorylated tyrosine kinase .

Detailed Description:
the following description and the corresponding embodiments of the present invention are set forth as preferred examples . it will be apparent to those skilled in the art that modifications , including additions and / or substitutions , may be made without departing from the scope and spirit of the invention . specific details may be omitted so as not to obscure the invention ; however , the disclosure is written to enable one skilled in the art to practice the teachings herein without undue experimentation . cytotoxicity effect of tms on gefitinib - resistant nsclc cells and normal lung epithelial cells is demonstrated by the cell viability assay . in fig1 , tms shows selectivity on gefitinib - resistant nsclc cells ( h1975 and h820 cell line ), while there is a lower ic 50 on normal cells ( beas - 2b cell line ) and other types of nsclc cells such as a549 and h358 which are egfr wild - type non - small - cell lung cancer cell lines . table 1 summarizes the ic 50 values of five different cell lines treated with tms . proteomics analysis results in fig3 show that mammalian target of rapamycin ( mtor ) is significantly inhibited by tms . moreover , activation of mtor pathway by compound c , where compound c is a well - known ampk inhibitor , and ampk is upstream of mtor counteracts the effect of tms , indicating that inhibition of mtor is required for tms to induce apoptosis in gefitinib - resistant nsclc cells . relative cell viability of gefitinib - resistant nsclc cells under different treatments is shown in fig4 . tms alone ( 40 nm ) is the most effective in inducing apoptosis in gefitinib - resistant nsclc cells among four different treatment groups in this example . fig5 shows that treatment of jnk inhibitor significantly blocks the apoptosis and cell death induced by tms , indicating that jnk activation is essential to tms - induced apoptosis in gefitinib - resistant nsclc cells . again , tms alone is the most effective in inducing apoptosis in gefitinib - resistant nsclc cells among four different treatment groups , as shown in fig6 fig7 shows that tms inhibits the activation of egfr py1173 in gefitinib - resistant nsclc cells , where egfr py1173 is an activation site of egfr and can further activate the downstream effector stat3 and stat5 , leading to an increase in cell proliferation . in this example , tms at 40 , 60 and 80 nm inhibits the activation of egfr py1173 in gefitinib - resistant nsclc cells significantly . moreover , the inhibition of py1173 activation happens as early as in 1 hour after tms treatment . interestingly , this inhibitory effect of tms on egfr is not detected in a549 cells , suggesting that tms is selective for killing nsclc cells that have egfr mutation and are resistant to current gefitinib treatment . even we used 10 - time higher concentration of tms to treat a549 , no suppression of egfr py1173 was observed , indicating tms is more effective in inhibiting h1975 . the present invention is useful in developing into pharmaceutical composition for treating patients with gefitinib - resistant nsclc which is difficult to treat by using the conventional therapies . the findings in the present invention also provide insight on developing specific and selective drug for gefitinib - resistant nsclc . the foregoing description of the present invention has been provided for the purposes of illustration and description . it is not intended to be exhaustive or to limit the invention to the precise forms disclosed . many modifications and variations will be apparent to the practitioner skilled in the art . the embodiments or examples are chosen and described in order to better explain the principles of the invention and its practical application , thereby enabling others skilled in the art to understand the invention for various embodiments and with various modifications that are suited to the particular use contemplated . it is intended that the scope of the invention be defined by the appended claims and their equivalence . the following references are also incorporated herein by reference in their entirety . 1 . gansler , t ., et al ., sixty years of ca : a cancer journal for clinicians . ca : a cancer journal for clinicians , 2010 . 60 ( 6 ): p . 345 - 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