Combination with SN-38 on human colon cancer LoVo cells / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To observe the anti-proliferation effect of bevacizumab and SN-38 (active metabolite of irinotecan), and investigate the possible mechanisms of these two agents.</p><p><b>METHODS</b>Human colon cancer LoVo cells were cultured under hypoxic conditions. Inhibition of cell proliferation was evaluated by MTT assay. The drug modulation on HIF-1alpha, VEGF, ERK and AKT were assessed by the following assays. The mRNA expression of HIF-1alpha and VEGF were measured by RT-PCR. The protein expression of HIF-1alpha, ERK and AKT were evaluated by Western blot analysis, and VEGF by ELISA assay.</p><p><b>RESULTS</b>Among different combination schedules, Bevacizumab given after SN-38 show most synergistic anti-proliferation effect. Under hypoxic conditions, the expression of HIF-1alpha and VEGF increased as time accumulated, Bevacizumab combined with SN-38 almost completely inhibited the expression of HIF-1alpha and VEGF. Moreover, the MAP kinase pathway was involved in the drug modulation of HIF-1alpha and VEGF.</p><p><b>CONCLUSION</b>These findings suggest the anti-proliferation effect of bevacizumab and SN-38 was schedule-dependent, and the synergistic effect of Bevacizumab and SN-38 was related to drug modulation of the HIF-1alpha and MAP kinase pathway.</p>

Effect of small interfering RNA-induced LKB1 gene silencing on the biological behavior of lung carcinoma cells / 南方医科大学学报

<p><b>OBJECTIVE</b>To study the effect of the small interfering RNA (siRNA)-mediated LKB1 gene silencing on the biological behavior of lung carcinoma cells.</p><p><b>METHODS</b>RNA interference technique was used to silence LKB1 gene in lung carcinoma cells, and the expression of LKB1 protein were subsequently detected by Western blotting. The cell proliferation was then assessed by observing the growth curve and clone formation of the cells, and cell cycle and apoptosis were assayed by flow cytometry.</p><p><b>RESULTS</b>LKB1 siRNA resulted in remarkable suppression of LKB1 expression in the lung carcinoma cells. LKB1 gene silencing resulted in accelerated cell proliferation, but cell apoptosis underwent no significant changes.</p><p><b>CONCLUSION</b>Down-regulation of LKB1 gene expression can stimulate malignant biological behavior of lung carcinoma cells.</p>

Effect of overexpression of Smad7 gene on cell proliferation / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To study the effect of overexpression of Smad7 gene on cell proliferation in human bronchial epithelial cell lines.</p><p><b>METHODS</b>Human bronchial epithelial cell lines, BEP2D and BERP35T2 cells, were cotransfected with the mammalian expression vectors PCISmad7.neo and pMyc-SEAP, the latter was ac-myc cis-acting enhancer element fused with alkaline phosphatase (SEAP) reporter gene. Expression of c-myc, p15 and p21 mRNA was detected by RT-PCR before and after stable transfection of Smad7 into BEP2D and BERP35T2 cells in order to study the regulation of TGF-beta-mediated growth inhibition.</p><p><b>RESULTS</b>After BEP2D and BERP35T2 cells transfected with Smad7, the transcriptional activity of c-myc was significantly increased. Smad7 overexpressing cells showed upregulation of c-myc expression and downregulation of p15 and p21 expression, which contributed to the loss of TGF-beta responses in these cells.</p><p><b>CONCLUSION</b>Overexpression of Smad7 may facilitate cell proliferation by antagonizing TGF-beta-mediated antiproliferative gene responses.</p>