HER-2 expression in local advanced breast cancer and the efficacy of neoadjuvant chemotherapy regimens / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the relationship between HER-2 expression and the efficacy of neoadjuvant chemotherapy in local advanced breast cancer.</p><p><b>METHODS</b>Different neoadjuvant chemotherapy regimens, namely CMF, CEF, and NEF, were administered in 132 patients with local advanced breast cancer for 2 cycles, each lasting for 28 days. According to the criteria recommended by WHO, the efficacy and safety of the regimens were evaluated after two cycles of neoadjuvant chemotherapy. HER-2 expression was examined by immunohistochemistry using specific monoclonal antibodies before chemotherapy and after surgery.</p><p><b>RESULTS</b>The overall response rate (RR) of CMF, CEF, and NEF regimens were 39.5% (17/43), 54.3% (25/46) and 72.1% (31/43), with incidence of leukopenia of 34.9% (15/43), 58.7% (27/46) and 60.5% (26/43), respectively. Other adverse effects including decreased hemoglobin (Hb) level, thrombocytopenia, gastrointestinal irritation and alopecia were similar between the 3 groups (P>0.05). No significant variation in HER-2 expression occurred after administration of the 3 regimens. The overall RR to CMF regimen in HER-2-negative breast cancer patients was significantly higher than that in HER-2-positive patients, but showed no significant difference with CEF and NEF regimens.</p><p><b>CONCLUSION</b>HER-2 expression is not decreased after neoadjuvant chemotherapy in breast cancer patients, and HER-2-positive breast cancer can be resistant to CMF regimen, but not to CEF and NEF regimens.</p>

Knockdown of survivin expression by small interfering RNA suppresses proliferation of two human cancer cell lines / 中国医学科学杂志(英文版)

<p><b>OBJECTIVE</b>To construct an expression vector of small interfering RNA (siRNA) against survivin and observe its effects on survivin expression and proliferation of human pancreatic cancer cell line PC-2 and breast cancer cell line MCF-7.</p><p><b>METHODS</b>Constructed an expression vector of siRNA against survivin and transfected it into PC-2 and MCF-7 cells using lipofectamine 2000. The expression of survivin was detected by semi-quantitive RT-PCR and immunohistochemistry, and its effects on proliferation of PC-2 and MCF-7 cells were detected by MTT assay.</p><p><b>RESULTS</b>The introduction of sequence-specific siRNA could efficiently suppress survivin expression at both mRNA and protein levels in the two cancer cell lines. In PC-2 cells, the expression inhibition rates were 81.25% at mRNA level and 74.24% at protein level. In MCF-7 cells, the expression inhibition rates were 64.91% at mRNA level and 79.72% at protein level. The proliferation of PC-2 and MCF-7 cells was also suppressed, and 24 and 48 hours after the cells were reseeded, the proliferation inhibition rates of PC-2 cells were 28.00% and 33.38%, and that of MCF-7 cells were 31.58% and 33.02%, respectively.</p><p><b>CONCLUSIONS</b>The expression vector of siRNA against survivin can block survivin expression in PC-2 and MCF-7 cells efficiently and specifically. Down regulation of survivin expression can suppress proliferation of PC-2 and MCF-7 cells. Survivin RNAi may have potential value in gene therapy of human cancers.</p>

siRNA targeted against survivin induces apoptosis of pancreatic cancer cells / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effect of a sequence-specific small interfering RNA (siRNA) in suppressing survivin expression and cell proliferation and inducing apoptosis of PC-2 cells.</p><p><b>METHODS</b>The plasmid expression vector of siRNA targeted against survivin was constructed and transfected into PC-2 cells with Lipofectamine 2000. The changes of survivin expression were detected by semi-quantitative RT-PCR and immunohistochemical SP methods. The effect of siRNA in suppressing the proliferation of PC-2 cells was detected by MTT assay, and its role in inducing PC-2 cell apoptosis evaluated by flow cytometry.</p><p><b>RESULTS</b>The sequence-specific siRNA effectively suppressed survivin expression at both mRNA and protein levels with inhibition rate of 81.25% at mRNA level and 74.24% at protein level. Survivin expression suppression significantly inhibited the proliferation of PC-2 cells, and at 24 and 48 h after cell seeding, the proliferation inhibition rate was 28.00% and 33.38% respectively; 24, 48 h after the transfection, apoptosis occurred in 8.46% and 7.53% of the cells, respectively.</p><p><b>CONCLUSIONS</b>The plasmid expression vector for the siRNA against survivin constructed in the study can effectively and specifically suppress survivin expression in PC-2 cells, and blocking survivin expression suppresses PC-2 cell proliferation and induces cell apoptosis. siRNA targeted against survivin has a potential value in gene therapy for pancreatic cancer.</p>

Effects of siRNA targeted to survivin in suppressing proliferation and inducing apoptosis in breast cancer MCF-7 cells / 中华肿瘤杂志

<p><b>OBJECTIVE</b>Blocking the expression of survivin with RNA interference techniques, the effects of suppressing proliferation and inducing apoptosis of breast cancer MCF-7 cells were investigated.</p><p><b>METHODS</b>A siRNA eukaryotic expression vector against survivin was constructed and transfected into breast cancer MCF-7 cells with lipofectamine 2000. The changes of survivin expression were detected by semi-quantitive RT-PCR and immunohistochemistry. The effect of suppressing proliferation of MCF-7 cell was detected by MTT assay. The effect of inducing MCF-7 cell apoptosis was detected by TUNEL assay.</p><p><b>RESULTS</b>The sequence-specific siRNA can efficiently block the expression of survivin both at mRNA and protein levels. The expression inhibition rate was 64.9% at mRNA level detected by semi-quantitive RT-PCR and 79.7% at protein level detected by immunohistochemistry. Blocking the expression of survivin can suppress proliferation of MCF-7 cells significantly. At 24 and 48 h after the cells were reseeded, the proliferation inhibition rates were 31.6% and 33.0%, respectively. At 24 h after transfection, apoptosis was induced in 12.9% of the cells as detected by TUNEL assay.</p><p><b>CONCLUSION</b>Blocking the expression of survivin with RNA interference technology can significantly suppress proliferation of MCF-7 cells and induce apoptosis to a certain degree. RNAi targeted to survivin has a potential value in gene therapy of breast cancer.</p>

Chemopreventive effect of celecoxib against DMBA-induced breast cancer and its mechanism / 南方医科大学学报

<p><b>OBJECTIVE</b>To evaluate the chemopreventive effect of celecoxib, a specific cyclooxegenease-2 (COX-2) inhibitor, on chemically induced breast cancer of rats and its effect on COX-2 expression.</p><p><b>METHODS</b>7, 12-dimethylbenz anthracene (DMBA) was administered intragastrically in SD female rats to establish breast cancer models, which were divided subsequently into control group, tamoxifen group and celecoxib group to receive different treatments accordingly. The occurrence rate of breast cancer was observed and the effect of celecoxib on COX-2 and vascular endothelial growth factor (VEGF) expressions assayed by immunohistochemical SP method.</p><p><b>RESULTS</b>The incidence of breast cancer in tamoxifen group (48.15%) and celecoxib group (50.00%) were both significantly lower than that in the control group (85.71%; P=0.003 and P=0.004, respectively). The positivity rate of COX-2 expression in celecoxib group (28.57%) was significantly lower than those of tamoxifen group (48.15%) and control group (83.33%; P=0.001 and P=0.035, respectively). The positivity rate of VEGF expression in celecoxib group (42.86%) was significantly lower than that of control group (79.17%, P=0.023), but comparable with that in tamoxifen group (46.15%, P=0.863).</p><p><b>CONCLUSION</b>Celecoxib can significantly suppress DMBA-induced breast cancer in female rats possibly through down-regulation of COX-2 and VEGF expressions.</p>