PTPRZ1通过调控PI3K/Akt通路促进乳腺癌细胞增殖和多西他赛耐药

目的:探讨蛋白酪氨酸磷酸酶受体Z1型(protein tyrosine phosphatase receptor type Z1,PTPRZ1)对人乳腺癌MCF-7细胞多西他赛耐药性的影响及其作用机制。方法:将MCF-7细胞暴露于逐渐增强浓度的多西他赛中建立对多西他赛耐药的乳腺癌细胞（MCF-7/Doc）。采用CCK-8法分别检测MCF-7和MCF-7/Doc细胞对多西他赛的耐药性。qRT-PCR和Western blot检测细胞中PTPRZ1 mRNA及蛋白表达水平。克隆形成实验检测细胞增殖情况，流式实验检测细胞凋亡情况。最后采用Western blot检测PTPRZ1调控乳腺癌化疗敏感性的作用机制。结果:CCK-8实验表明成功构建了乳腺癌多西他赛耐药细胞株MCF-7/Doc，克隆形成实验表明MCF-7/Doc细胞增殖能力显著高于亲本MCF-7细胞（P＜0.05）；MCF-7/Doc细胞中，PTPRZ1 mRNA及蛋白水平均显著上调（P＜0.05）。过表达PTPRZ1能显著增强MCF-7/Doc细胞对多西他赛的耐药性和增殖能力，显著抑制细胞凋亡（P＜0.05）；敲减PTPRZ1能显著降低MCF-7/Doc细胞对多西他赛的耐药性，并能显著诱导细胞凋亡（P＜0.05）。Western blot结果显示，PTPRZ1能够激活PI3K/Akt信号通路。结论:PTPRZ1通过介导PI3K/Akt信号通路促进乳腺癌对多西他赛的耐药性。

PTPRZ1 promotes breast cancer cell proliferation and docetaxel-resistance by regulating the PI3K/Akt pathway

Objective:To investigate the effect of protein tyrosine phosphatase receptor type Z1 (PTPRZ1) on docetaxel-resistance in human breast cancer MCF-7 cells and its mechanism.Methods:MCF-7 cells were exposed to increasing concentrations of docetaxel to establish docetaxel-resistant breast cancer cells (MCF-7/Doc).The resistance of MCF-7 and MCF-7/Doc cells to docetaxel was measured by CCK-8 method.qRT-PCR and Western blot were used to detect the mRNA and protein expression levels of PTPRZ1 in cells.The cell proliferation was detected by colony formation assay,and the cell apoptosis was detected by flow cytometry.Finally,Western blot was used to detect the mechanism of PTPRZ1 regulating the chemosensitivity of breast cancer.Results:CCK-8 experiments showed that the docetaxel resistant cell line MCF-7/Doc was successfully constructed.The colony formation assay showed that the proliferation of MCF-7/Doc cells was significantly higher than that of the parental MCF-7 cells (P＜0.05).In MCF-7/Doc cells,the mRNA and protein levels of PTPRZ1 were significantly up-regulated (P＜0.05).Overexpression of PTPRZ1 significantly enhanced the resistance and proliferation of MCF-7/Doc cells to docetaxel and significantly inhibited apoptosis (P＜0.05).Knockdown of PTPRZ1 significantly reduced the resistance of MCF-7/Doc cells to docetaxel and significantly induced apoptosis (P＜0.05).Western blot results showed that PTPRZ1 activated the PI3K/Akt signaling pathway.Conclusion:PTPRZ1 promotes the resistance of breast cancer to docetaxel by mediating the PI3K/Akt signaling pathway.