SH3GL1在紫杉醇耐药乳腺癌中的表达及临床意义

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

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.

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.