The likely detrimental effects that tamoxifen has on individuals in danger of

Statistical analysis Statistical supplier INNO-406 comparison was made using GraphPad Prism software in which one way analysis of variance and Tukeys multiple comparison post tests were used to determine significant differences between several treatment groups. Students paired t test was used when only two groups were compared. Data are presented as mean S. E. M. of at least three independent experiments with tripli cate. Statistical significance was evaluated by calculating P values. Differences where P 0. 05 were considered statis tically significant, Results Effect of P276 00 and doxorubicin on cell proliferation Three NSCLC cell lines H 460, H1299 and H23 were treated with increasing concentrations of P276 00 for 72 h and cell proliferation was assessed.<br><br> Treatment with P276 00 caused a dose dependent de crease in the proliferation of all the three cell lines, Thus, P276 00 was an effective inhibitor of NSCLC cancer cell supplier Lapatinib growth as a single agent, and H 460 and H1299 were more sensitive than H23 as seen from the IC50 values, Doxorubicin was also effect ive as a single agent and H 460 was highly sensitive to doxorubicin while H1299 and H23 were moderately sen sitive, P276 00 potentiates growth inhibition induced by doxorubicin in various human NSCLC cell lines The anthracycline antibiotic doxorubicin is commonly used in lung cancer treatment regimens. However, in contrast to its high activity in SCLC, doxorubicin is not curative in NSCLC which represents 4 5 of all lung can cers, To determine if P276 00 enhances the sensitiv ity of NSCLC cells to the growth inhibitory effect of doxorubicin, combination studies were done.<br><br> Cells were either treated with P276 00 or doxorubicin or in combination with serial concentra tions of doxorubicin followed by P276 00 for 72 h and cell viability was evalu ated. Combination treatment Lonafarnib 価格 yielded significantly greater growth inhibition in a dose dependent manner than ei ther agent alone in all three cell lines, The combination index method developed by Chou was used to confirm and quantify the synergism observed with doxorubicin and P276 00. The CI values of the combination of IC50 of P276 00 with various concentra tion of doxorubicin were calculated using CompuSyn software. The p53 positive H 460 and p53 mutant H 23 cell lines showed synergism with CI range of 0. 63 0. 94 and 0. 86 0. 9 respectively.<br><br> The combination of doxorubi cin followed by P276 00 was not synergistic in the p53 null H1299 cell line. For all further studies, H 460 cell line was selected, which possesses wild type p53 gene, mutant KRAS and wild type EGFR, Synergistic cytotoxicity of doxorubicin and P276 00 combination is due to increased apoptosis We observed induction of apoptosis in H 460 cells trea ted with either doxorubicin or P276 00 or both, Relative to single agents, the combination treatment induced more apoptosis as shown in Figure 2C and 2D, In fact, doxo rubicin induced G2 M arrest, which was overcome by subsequent P276 00 treatment. These results are con sistent with cell growth inhibition studies. The combin ation of 100 nM doxorubicin followed by 1200 nM of P276 00 for 72 h was found to be the most synergistic and hence used for further mechanistic studies.