Department of Trauma Surgery, Affiliated Hospital of Qingdao University, Qingdao, Shandong 266000, P.R. China.
Department of Joint Surgery, Affiliated Hospital of Qingdao University, Qingdao, Shandong 266000, P.R. China.
Mol Med Rep. 2017 Aug;16(2):1701-1706. doi: 10.3892/mmr.2017.6828. Epub 2017 Jun 21.
Anaberrant Wnt/β-catenin signaling pathway is frequently implicated in tumorigenesis. However, whether the Wnt/β‑catenin pathway plays a role in resistance to antitumor chemotherapy drugs remains unknown. In the present study, the process of autophagy was assessed following overexpression of the autophagy‑associated gene Beclin 1 in gemcitabine‑induced MG63 human osteosarcoma cells. Autophagy‑associated gene expression was measured following activation or inhibition of the Wnt/β‑catenin pathway in gemcitabine‑induced MG63 cells using reverse transcription‑quantitative polymerase chain reaction. In addition, the percentage of MG63 cell apoptosis was measured by flow cytometry following Wnt/β‑catenin pathway activation or inhibition. The results demonstrated that Beclin 1 overexpression induced autophagy and reduced gemcitabine‑induced apoptosis in MG63 human cell line. Furthermore, activation of the Wnt/β‑catenin signaling pathway attenuated autophagy and enhanced gemcitabine‑induced apoptosis. Additionally, the expression of Beclin 1 was reduced following Wnt/β‑catenin signaling pathway activation. The present study demonstrated that activation of the Wnt/β‑catenin signaling pathway may rescue chemotherapy drug resistance by downregulating the expression of Beclin 1.
异常的 Wnt/β-连环蛋白信号通路常与肿瘤发生有关。然而，Wnt/β-连环蛋白通路是否在抗肿瘤化疗药物耐药中发挥作用尚不清楚。在本研究中，在吉西他滨诱导的 MG63 人骨肉瘤细胞中转染自噬相关基因 Beclin 1 后，评估了自噬过程。使用逆转录-定量聚合酶链反应，在吉西他滨诱导的 MG63 细胞中激活或抑制 Wnt/β-连环蛋白通路后，测量自噬相关基因的表达。此外，通过流式细胞术测量 Wnt/β-连环蛋白通路激活或抑制后 MG63 细胞的凋亡百分比。结果表明，Beclin 1 的过表达诱导了自噬，并减少了吉西他滨诱导的 MG63 人细胞系中的细胞凋亡。此外，Wnt/β-连环蛋白信号通路的激活减弱了自噬并增强了吉西他滨诱导的细胞凋亡。此外，Wnt/β-连环蛋白信号通路的激活后 Beclin 1 的表达减少。本研究表明，Wnt/β-连环蛋白信号通路的激活可能通过下调 Beclin 1 的表达来挽救化疗药物耐药。
