Research Progress of Autophagy in the Development and Treatment of Bladder Cancer
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摘要: 自噬是细胞通过溶酶体降解细胞内物质的一种自我消化过程,被认为是肿瘤在应激条件下维持生存的重要保护机制。大量证据表明,自噬是一把双刃剑,通过不同的信号通路,既可抑制肿瘤的发生,又可促进肿瘤的存活与生长。因此,越来越多的学者认为自噬有望成为肿瘤治疗的新策略。通过总结自噬调控膀胱癌侵袭、转移等生物学行为,以及在膀胱癌治疗的最新进展,以期为靶向自噬抗肿瘤药物的研发和治疗提供新的思路。Abstract: Autophagy is a self-digestive process of cells degrading intracellular substances through lysosomes and is considered to be an important protection mechanism for tumors to maintain survival under stress conditions. A large number of evidence shows that autophagy is a double-edged sword, which can suppress the occurrence of tumors and promote the survival and growth of tumors by different signaling pathways. Therefore, more and more scholars believe that autophagy is expected to become a new strategy for tumor treatment. This paper summarizes the biological behavior of autophagy regulation of bladder cancer invasion, metastasis, and the latest progress in the treatment of bladder cancer and provides new ideas for the development and treatment of autophagy-targeted antitumor drugs.
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Key words:
- Bladder cancer /
- Autophagy /
- Tumor therapy /
- Drug resistance
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表 1 自噬与膀胱癌发展
Table 1. Autophagy and the development of bladder cancer
靶标 信号通路 自噬状态 肿瘤调控 砷 不确定 自噬缺陷 肿瘤发生 Rab14 MAPK/ERK 抑制 肿瘤发生 MIR-516A PHLPP2/BECN1 抑制 肿瘤发生 低营养 TGF-β1/Smad3 激活 上皮间质转化 MIR-21 不确定 抑制 上皮间质转化 缺氧 不确定 激活 血管生成 肿瘤微环境 PI3K/AKT 激活 血管生成 顺铂 BECN1 激活 化疗耐药 吡柔比星 p70S6K/4E-BP1 激活 化疗耐药 IFN-γ JAK2/STAT3 激活 干性维持 ATG7 USP28/CD44 激活 干性维持 NBR1 Not determined 激活 免疫逃逸 ATG7 FOXO3a/miR-145/PD-L1 激活 免疫逃逸 表 2 膀胱癌中的靶向自噬治疗
Table 2. Targeted autophagy therapy in bladder cancer
类型 治疗物质 自噬状态 调控作用 测试细胞系 天然活性物质 没食子酸酯 激活 凋亡 T24.5637 桦木酸 激活 凋亡 T24.EJ 灵菌红素 抑制 化疗敏感 RT-112 小分子化合药 罗帕洛酸 激活 凋亡 T24.J82 甲磺酸 抑制 化疗敏感 5637.HT1197 厄达替尼 激活 凋亡 T24.UMUC-3 非编码RNA MIR-24-3p 激活 肿瘤发展 T24.BIU-87 MIR-222 抑制 化疗敏感 T24.5637 ADAMTS9-AS2 激活 凋亡 5637.UM-UC-3 其他 重组腺病毒 激活 凋亡 T24.5637.EJ 重组精氨酸酶 激活 凋亡 T24.5637.J82 -
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