雌激素受体-α36(ER-α36)介导乳腺癌细胞的顺铂耐药性

Estrogen Receptor-α36(ER-α36) Mediates Cisplatin Resistance in Breast Cancer Cells

雌激素受体-α36(estrogen receptor-α36,ER-α36)在乳腺癌细胞中对顺铂耐药性的作用和机制尚不清楚。本研究考察了ER-α36在乳腺癌细胞中的表达及ER-α36对顺铂耐药性的影响和机制。Western blotting分析显示,顺铂诱导人乳腺癌细胞MCF-7中ER-α36的上调。细胞计数8试剂盒(cell counting kit-8,CCK-8)和细胞集落形成实验显示,过表达ER-α36显著提高了MCF-7细胞的增殖能力和集落形成能力,而敲低ER-α36则可抑制MCF-7细胞的增殖能力和集落形成能力。5μg/mL顺铂处理可激活EGFR/HER-2/ERK信号。敲低ER-α36可显著抑制MCF-7/DDP或MCF-7/ER-α36细胞中EGFR/HER-2/ERK信号的激活。抑制EGFR/HER-2/ERK信号可降低MCF-7/ER-α36细胞的增殖能力。总之,本研究证明ER-α36的上调通过激活EGFR/HER-2/ERK信号提高了乳腺癌细胞的顺铂耐药性。靶向ER-α36可能是提高顺铂敏感性的有效策略。

The role and mechanism of estrogen receptor-α36(ER-α36)in cisplatin resistance in breast cancer cells is still unclear.This study investigated the expression of ER-α36 in breast cancer cells and the effect and mechanism of ER-α36 on cisplatin resistance.Western blotting analysis showed that cisplatin induced up-regulation of ER-α36 in breast cancer cells MCF-7.Cell counting kit-8(CCK-8)and cell colony formation experiments showed that overexpression of ER-α36 significantly promoted the proliferation and colony forming ability of MCF-7 cells,while knockdown of ER-α36 inhibited the proliferation and colony forming ability of MCF-7 cells.Treatment with 5μg/mL cisplatin activated the EGFR/HER-2/ERK signal.Knockdown of ER-α36 significantly inhibited the activation of EGFR/HER-2/ERK signaling in MCF-7/DDP or MCF-7/ER-α36 cells.Inhibition of EGFR/HER-2/ERK signaling reduced the proliferation of MCF-7/ER-α36 cells.In conclusion,this study demonstrates that upregulation of ER-α36 increases cisplatin resistance in breast cancer cells by activating EGFR/HER-2/ERK signaling.Targeting ER-α36 may be an effective strategy to increase cisplatin sensitivity.