Department of Radiotherapy, Gansu Provincial Hospital, Lanzhou, Gansu 730050, P.R. China.
Department of Physical Examination Center, The Third People's Hospital of Gansu, Lanzhou, Gansu 730050, P.R. China.
Mol Med Rep. 2017 Dec;16(6):8747-8754. doi: 10.3892/mmr.2017.7721. Epub 2017 Oct 4.
With regards to colon cancer, resistance to 5‑fluorouracil (5‑FU)‑based chemotherapy and cancer stem cells (CSCs) are considered important factors underlying therapy failure. Metastasis‑associated colon cancer 1 (MACC1) has been associated with poor prognosis and the promotion of metastasis within several types of cancer. However, the biological behavior of MACC1 in chemoresistance and CSC‑like properties remains unclear. In the present study, various methods including gene knockdown, gene overexpression, western blotting, quantitative polymerase chain reaction and MTT assay, have been adopted. According to the results of the present study, MACC1 was depleted in two colon cancer cell lines resistant to 5‑FU; subsequently, CSC‑like properties and 5‑FU sensitivity were investigated. Within 5‑FU‑resistant cells, cell death was facilitated by MACC1 knockdown. Furthermore, sphere formation and the expression levels of pluripotent markers, including cluster of differentiation (CD) 44, CD133 and Nanog were reduced due to MACC1 depletion. Additionally, it was indicated that the phosphoinositide 3‑kinase/protein kinase B signaling pathway may be associated with 5‑FU resistance and CSC‑like properties via MACC1.
关于结肠癌，对 5-氟尿嘧啶（5-FU）为基础的化疗和癌症干细胞（CSC）的耐药性被认为是治疗失败的重要因素。转移相关结肠癌 1（MACC1）与多种癌症的预后不良和转移促进有关。然而，MACC1 在化疗耐药性和 CSC 样特性中的生物学行为尚不清楚。在本研究中，采用了基因敲低、基因过表达、western blot、定量聚合酶链反应和 MTT 检测等各种方法。根据本研究的结果，在对 5-FU 耐药的两种结肠癌细胞系中耗尽了 MACC1；随后，研究了 CSC 样特性和 5-FU 敏感性。在 5-FU 耐药细胞中，MACC1 敲低促进细胞死亡。此外，由于 MACC1 的耗竭，球体形成和多能标志物（包括分化簇（CD）44、CD133 和 Nanog）的表达水平降低。此外，还表明磷酸肌醇 3-激酶/蛋白激酶 B 信号通路可能通过 MACC1 与 5-FU 耐药性和 CSC 样特性相关。
