克里普托坦辛在缺乏ATP6V0D1的胰腺癌细胞中差异诱导细胞死亡

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Fangquan Chen¹, Junhao Lin¹, Xiutao Cai¹

¹DAMP Laboratory, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou 510150, Guangdong, China.

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概括

在胰腺癌中,ATPase H+运输V0亚单元D1 (ATP6V0D1) 的遗传淘汰激活了瘤性STAT3和AKT通路. 针对这些通路和FGFR2可能提供针对ATP6V0D1缺乏PDAC的治疗策略.

科学领域:

在瘤学瘤学.
分子生物学分子生物学
癌症信号传递癌症信号传递

背景情况:

瘤抑制剂的调节失调激活了瘤性途径,创造了治疗脆弱性.
酸酶H+运输V0亚单元D1 (ATP6V0D1) 是化酶的关键媒介.
缺少ATP6V0D1导致STAT3和AKT信号通路的过度激活.

研究的目的:

研究ATP6V0D1缺乏如何重塑瘤信号网络和胰腺管道腺癌 (PDAC) 中的细胞异质性.
评估治疗策略,以向PDAC中与化相关的脆弱性.

主要方法:

通过基因敲除生成的ATP6V0D1缺乏的胰腺癌细胞 (SW1990,MIAPaCa2).
通过CCK-8和化测定来评估细胞活力和死亡.
进行了转录基因分析,西部抹杀和巨细胞分析;分析了DepMap数据库.

主要成果:

ATP6V0D1删除导致STAT3和AKT信号的过度激活,通过途径抑制逆转,恢复化.
在ATP6V0D1缺乏的MIAPaCa2细胞中,Cryptotanshinone选择性诱导细胞死亡,但不是SW1990细胞.
在SW1990细胞中的抵抗与FGFR2上调有关,由FGFR2抑制逆转.

结论:

ATP6V0D1缺陷通过补偿性STAT3/AKT信号和FGFR2-介导的异质性促进PDAC进展.
准STAT3,AKT和FGFR2通路为PDAC提供了潜在的治疗途径.
瘤异质性仍然是开发有效的PDAC疗法的重大临床挑战.

关键词:

在 ATP6V0D1 中,细胞死亡是细胞死亡.没有任何的cryptotanshinone.瘤异质性的异质性

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