Department of Laboratory Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, P.R. China.
Department of Hepatobiliary Surgery, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, P.R. China.
Int J Mol Med. 2020 Jun;45(6):1838-1850. doi: 10.3892/ijmm.2020.4543. Epub 2020 Mar 16.
Resistance to the chemotherapeutic drug cisplatin has been documented in various types of cancer, while the increased expression of β‑catenin has been observed in cisplatin‑resistant ovarian cancer. However, the involvement of β‑catenin in cisplatin resistance is unclear. The present study investigated the antitumor effect of cisplatin on the proliferation, invasion and apoptosis of breast cancer (BC) cells following β‑catenin silencing in BC, which is the most frequent type of malignancy among women. The expression of β‑catenin in BC tissues and cell lines was measured by reverse transcription‑quantitative polymerase chain reaction, and the association between expression levels and clinical characteristics was statistically analyzed. The viability of BC cell lines treated with siR‑β‑catenin or with siR‑β‑catenin and cisplatin in combination was determined using a Cell Counting Kit‑8 assay. The migratory and invasive abilities of BC cells treated with both siR‑β‑catenin and cisplatin were examined with Transwell assays. The CD44 antigen/intercellular adhesion molecule 1 expression ratio, cell cycle distribution and apoptosis levels of BC cells treated with siR‑β‑catenin and cisplatin in combination were detected by flow cytometry. The expression levels of apoptosis‑associated proteins, including caspase‑3/9, in the BC cells treated with both siR‑β‑catenin and cisplatin were investigated by western blot analysis. The levels of apoptosis in the BC cells following combined treatment with siR‑β‑catenin and cisplatin was further quantified by Hoechst 33342 staining. β‑catenin was identified to be highly expressed in BC tissues and cell lines and was associated with pathological stage and lymph node status. Following knockdown of β‑catenin expression, cisplatin treatment suppressed the viabilities, and the migratory and invasive capabilities of the T47D and MCF‑7 cells, and induced extensive apoptosis. β‑catenin knockdown upregulated caspase‑3/9 levels following cisplatin treatment and induced the apoptosis of T47D and MCF‑7 cells. In conclusion, β‑catenin may be of value as a therapeutic target during cisplatin treatment in patients with BC treated with cisplatin.
耐药性顺铂的化学治疗药物已在各种类型的癌症中得到证实,而β-连环蛋白的表达增加已在顺铂耐药性卵巢癌中观察到。然而,β-连环蛋白在顺铂耐药性中的作用尚不清楚。本研究探讨了沉默乳腺癌(BC)细胞中的β-连环蛋白后,顺铂对BC细胞增殖、侵袭和凋亡的抗肿瘤作用,BC 是女性中最常见的恶性肿瘤类型。通过逆转录-定量聚合酶链反应测量 BC 组织和细胞系中的β-连环蛋白表达,并对表达水平与临床特征之间的关系进行统计学分析。通过细胞计数试剂盒-8 测定法测定用 siR-β-连环蛋白或用 siR-β-连环蛋白和顺铂联合处理的 BC 细胞系的活力。用 Transwell 测定法检测用 siR-β-连环蛋白和顺铂处理的 BC 细胞的迁移和侵袭能力。通过流式细胞术检测用 siR-β-连环蛋白和顺铂联合处理的 BC 细胞的 CD44 抗原/细胞间黏附分子 1 表达比、细胞周期分布和凋亡水平。通过 Western blot 分析研究用 siR-β-连环蛋白和顺铂处理的 BC 细胞中凋亡相关蛋白(包括 caspase-3/9)的表达水平。通过 Hoechst 33342 染色进一步定量分析用 siR-β-连环蛋白和顺铂联合处理后 BC 细胞的凋亡水平。β-连环蛋白在 BC 组织和细胞系中高表达,与病理分期和淋巴结状态有关。沉默β-连环蛋白表达后,顺铂处理抑制了 T47D 和 MCF-7 细胞的活力、迁移和侵袭能力,并诱导广泛的凋亡。β-连环蛋白敲低后,顺铂处理上调 caspase-3/9 水平,并诱导 T47D 和 MCF-7 细胞凋亡。综上所述,β-连环蛋白可能作为顺铂治疗的治疗靶点,用于治疗接受顺铂治疗的 BC 患者。