Department of Medical Oncology, Yantaishan Hospital, Yantai, China.
Department of Oncology, The Center Hospital of Zaozhuang Mining Group, Zaozhuang, China.
Cancer Biother Radiopharm. 2022 Nov;37(9):792-801. doi: 10.1089/cbr.2019.3390. Epub 2020 Jun 9.
Ovarian cancer is the public health issue worldwide. Paclitaxel is a first-line chemotherapy drug for ovarian cancer, but paclitaxel resistance weakens the therapeutic effect. Metformin (Met) improved the paclitaxel sensitivity in a mouse model of ovarian cancer. However, the mechanism of Met on paclitaxel sensitivity is still unclear in ovarian cancer. Cell viability, apoptosis, migration, and invasion were measured by Cell Counting Kit-8 (CCK8), flow cytometry, and transwell assays severally. The expression of long noncoding RNA (lncRNA) small nucleolar RNA host gene 7 (SNHG7) and microRNA-3127-5p (miR-3127-5p) were detected by real-time quantitative polymerase chain reaction. The protein levels of poly (ADP-ribose) polymerase, microtubule-associated protein 1 light chain 3 (LC3)-I, LC3-II, and Beclin 1 were examined by Western blot assay. RNA immunoprecipitation assay detected the relationship between SNHG7 and miR-3127-5p. Then, the binding correlation between SNHG7 and miR-3127-5p was predicted by starBase and verified by the dual-luciferase reporter. The effects of Met and SNHG7 on tumor growth were tested in ovarian cancer mice model. Met inhibited cell viability, migration, invasion, SNHG7 level, and autophagy and promoted apoptosis in paclitaxel-resistant ovarian cancer cells. Moreover, Met partly reversed SNHG7-mediated paclitaxel sensitivity and autophagy in ovarian cancer cells. SNHG7 directly bound to miR-3127-5p. Met abolished the promoting effect of SNHG7 overexpression on tumor growth and autophagy . The authors' findings indicated that Met expedited paclitaxel sensitivity by regulating SNHG7/miR-3127-5p-mediated autophagy in ovarian cancer cells.
卵巢癌是全球公共卫生问题。紫杉醇是卵巢癌的一线化疗药物，但紫杉醇耐药性削弱了治疗效果。二甲双胍（Met）可提高卵巢癌荷瘤小鼠模型对紫杉醇的敏感性。然而，Met 提高卵巢癌细胞对紫杉醇敏感性的机制尚不清楚。分别通过细胞计数试剂盒-8（CCK8）、流式细胞术和 Transwell 测定细胞活力、凋亡、迁移和侵袭。实时定量聚合酶链反应检测长链非编码 RNA（lncRNA）小核仁 RNA 宿主基因 7（SNHG7）和 microRNA-3127-5p（miR-3127-5p）的表达。Western blot 检测多聚（ADP-核糖）聚合酶、微管相关蛋白 1 轻链 3（LC3）-I、LC3-II 和 Beclin 1 的蛋白水平。RNA 免疫沉淀检测 SNHG7 与 miR-3127-5p 的关系。然后，通过 starBase 预测 SNHG7 与 miR-3127-5p 的结合相关性，并通过双荧光素酶报告验证。在卵巢癌小鼠模型中检测 Met 和 SNHG7 对肿瘤生长的影响。Met 抑制紫杉醇耐药卵巢癌细胞的活力、迁移、侵袭、SNHG7 水平和自噬，并促进凋亡。此外，Met 部分逆转了 SNHG7 介导的卵巢癌细胞紫杉醇敏感性和自噬。SNHG7 直接与 miR-3127-5p 结合。Met 消除了 SNHG7 过表达对肿瘤生长和自噬的促进作用。作者的研究结果表明，Met 通过调节 SNHG7/miR-3127-5p 介导的自噬来加速卵巢癌细胞对紫杉醇的敏感性。
