Silencing RRM1 gene reverses paclitaxel resistance in human breast cancer cell line MCF- 7/R by inducing cell apoptosis / 南方医科大学学报

OBJECTIVE@#To investigate the effects of ribonucleotide reductase catalytic subunit M1 (RRM1) gene silencing on drug resistance of human breast cancer cell line MCF-7/R.@*METHODS@#We established a paclitaxel-resistant breast cancer MCF-7 cell line (MCF-7/R) by exposing the cells to high-concentration paclitaxel in a short time. Small interfering RNAs (siRNAs) targeting RRM1 were designed to silence RRM1 expression in human breast cancer MCF-7/R cells. MTT assay was used to detect the IC values and the sensitivity to paclitaxel in the cells with or without siRNA transfection. The changes in the proliferative activity of MCF7 and MCF-7/R cells following RRM1 gene silencing were evaluated using EdU assay. Flow cytometry was used to analyze the cell apoptosis and cell cycle changes. We assessed the effect of RRM1 gene silencing and paclitaxel on the tumor growth in a nude mouse model bearing subcutaneous xenografts with or without siRNA transfection.@*RESULTS@#We detected significantly higher expressions of RRM1 at both the mRNA and protein levels in the drug-resistant MCF- 7/R cells than in the parental MCF-7 cells ( < 0.01). Transfection with the specific siRNAs significantly reduced the expression of RRM1 in MCF-7/R cells ( < 0.05), which showed a significantly lower IC value of paclitaxel than the cells transfected with the negative control siRNA ( < 0.05). RRM1 silencing significantly inhibited the proliferation ( < 0.01) and enhanced the apoptosis-inducing effect of paclitaxel in MCF-7/R cells ( < 0.001); RRM1 silencing also resulted in obviously reduced Akt phosphorylation, suppressed Bcl-2 expression and promoted the expression of p53 protein in MCF-7/R cells. In the tumor-bearing nude mice, the volume of subcutaneously transplanted tumors was significantly smaller in MCF-7/R/siRNA+ PTX group than in the other groups ( < 0.001).@*CONCLUSIONS@#RRM1 gene silencing can reverse paclitaxel resistance in human breast cancer cell line MCF-7/R by promoting cell apoptosis.

Structural and functional characterization of snake venom disintegrins / 中国药理学通报

According to their polypeptide length and number of d is ulphide bonds, disintegrins are divided into five groups, including short-sized disintegrins, medium-sized disintegrins, long-sized disintegrins, dimeric dis integrins and disintegrin-like molecules released from the disintegrin-like do mains of P-III snake venom metalloproteinases. The integrin-inhibitory activit y of disintegrins, to inhibit platelet aggregating, cell attaching and angiogene sis, depends on the active tripeptide RGD, the appropriate pairing of cysteine r esidues, the amino acids adjacent to the RGD motif within the integrin-binding loop and the C-terminus of the disintegrin polypeptidesl as well.