SH3GL1在紫杉醇耐药乳腺癌中的表达及临床意义

膜结合蛋白SH3GL1参与调控某些肿瘤细胞生物学行为，而其对紫杉醇耐药乳腺癌细胞的恶性生物学行为影响尚未见报道.为阐明 SH3GL1对紫杉醇耐药敏感性的影响以及潜在的分子机制，本研究首先采用免疫组化法证实SH3GL1在紫杉醇耐药乳腺癌组织高表达(P<0.001).Western印迹法证实,SH3GL1在紫杉醇耐药细胞株MCF-7/PTX高表达(P<0.01)；随后，采用MTT分别检测（0，50，100 nmol/L）紫杉醇处理后MCF-7细胞株增殖情况，同时Western印迹法检测SH3GL1表达，发现100 nmol/L紫杉醇能够抑制MCF-7细胞增殖(P<0.05)；同时抑制SH3GL1表达(P<0.01); 敲减SH3GL1表达后，紫杉醇耐药细胞株MCF-7/PTX和MCF-7增殖速率降低(P<0.05)，耐药基因MDR1表达降低(P<0.05)，p-AKT和p-gp水平下降(P<0.05).上述结果表明,降低SH3GL1表达可以减弱紫杉醇耐药性，增加乳腺癌对紫杉醇的敏感性，这为临床上紫杉醇耐药乳腺癌患者的治疗提供了新的靶点.

The Clinical Implication of SH3GL1 Expression in Paclitaxel-resistance Breast Cancer

SH3GL1 has been shown to regulate the biological behaviors of cancer cells. However, the role of SH3GL1 in the malignant paclitaxel-resistance cells remained unclear. We found that SH3GL1 was high-expressed in paclitaxel-resistance breast cancer tissues as compared to chemo sensitive tissues in immunohistochemistry. The SH3GL1 level was higher in MCF-7/PTX than MCF-7 cells in Western blot. The proliferative of MCF-7 cells following 0，50，100 nmol/L paclitaxel treatments was reduced. The SH3GL1 expression was suppressed in 100 nmol/L paclitaxel (P<0.05). SH3GL1 knockdown remarkably reduced the proliferation and the expression of MDR1, p-gp and p-AKT in both MCF-7 and MCF-7/PTX cells (P<0.05). Our results suggested that suppressing SH3GL1 could reduce the paclitaxel resistance and increase drug sensitivity in breast cancers.