Department of Medical Oncology, The Second Hospital of Dalian Medical University, Dalian, Liaoning, 116023, China.
Acute abdominal department, The Second Hospital of Dalian Medical University, Dalian, Liaoning, 116023, China.
Biomed Pharmacother. 2020 May;125:109961. doi: 10.1016/j.biopha.2020.109961. Epub 2020 Feb 3.
Gastric cancer (GC) is a malignant tumor originated from the epithelium of gastric mucosa, its incidence is second only to lung cancer in China. Chemotherapy is one of the most effective methods to treat GC, but some patients are insensitive to chemotherapeutic drugs, leading to chemotherapy failure. In this study, the expression of FAM83H-AS1 was up-regulated in GC tissues and cell lines, and was related to differentiation, invasion depth and chemotherapy insensitivity of GC patients. FAM83H-AS1 was high-expressed in chemoresistant GC tissues and cell line (SGC7901/R), and silence of FAM83H-AS1 sensitized SGC7901/R cells to cisplatin (CDDP) and 5-fluorouracil (5-FU). In addition, silence of FAM83H-AS1 could inactivate Wnt/β-catenin signaling pathway in SGC7901/R cells. The activating of Wnt/β-catenin signaling pathway reversed the promoting effect of FAM83H-AS1 silence on chemotherapy sensitivity, which meant Wnt/β-catenin signaling pathway mediated the regulation of FAM83H-AS1 on chemotherapy sensitivity in SGC7901/R cells. In conclusion, FAM83H-AS1 is related with the CDDP and 5-FU insensitivity of GC patients, silence of FAM83H-AS1 promotes chemosensitivity of GC through Wnt/β-catenin signaling pathway.
胃癌(GC)是一种起源于胃黏膜上皮的恶性肿瘤,其发病率在中国仅次于肺癌。化疗是治疗 GC 最有效的方法之一,但有些患者对化疗药物不敏感,导致化疗失败。在本研究中,FAM83H-AS1 在 GC 组织和细胞系中表达上调,与 GC 患者的分化、浸润深度和化疗不敏感性有关。FAM83H-AS1 在耐药性 GC 组织和细胞系(SGC7901/R)中高表达,沉默 FAM83H-AS1 可使 SGC7901/R 细胞对顺铂(CDDP)和 5-氟尿嘧啶(5-FU)敏感。此外,沉默 FAM83H-AS1 可使 SGC7901/R 细胞中的 Wnt/β-catenin 信号通路失活。Wnt/β-catenin 信号通路的激活逆转了 FAM83H-AS1 沉默对化疗敏感性的促进作用,这意味着 Wnt/β-catenin 信号通路介导了 FAM83H-AS1 对 SGC7901/R 细胞化疗敏感性的调节。总之,FAM83H-AS1 与 GC 患者对 CDDP 和 5-FU 的不敏感性有关,沉默 FAM83H-AS1 通过 Wnt/β-catenin 信号通路促进 GC 的化疗敏感性。