Lentinan exerts synergistic apoptotic effects with paclitaxel in A549 cells via activating ROS-TXNIP-NLRP3 inflammasome.
Lentinan exerts synergistic apoptotic effects with paclitaxel in A549 cells via activating ROS-TXNIP-NLRP3 inflammasome.
复制标题
香菇多糖通过激活ROS-TXNIP-NLRP3炎症小体与紫杉醇在A549细胞中发挥协同凋亡作用
DOI：
10.1111/jcmm.12570
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发表时间：
2015-08
影响因子：
5.3
通讯作者：
Sun XL
中科院分区：
文献类型：
--
作者：
Liu W;Gu J;Qi J;Zeng XN;Ji J;Chen ZZ;Sun XL
紫杉醇通常作为细胞分裂抑制剂在临床上用于治疗癌症。然而，肿瘤中的获得性耐药性限制了其临床疗效。因此，本研究的目的是检测是否与香菇多糖共同处理增强紫杉醇在A549细胞中的抗癌作用。我们发现，紫杉醇和香菇多糖的组合导致对A549细胞增殖的抑制比单独紫杉醇处理显著更强。紫杉醇和香菇多糖联合处理通过诱导caspase-3活化提高细胞凋亡率。此外，紫杉醇和香菇多糖的共同治疗显着触发活性氧（ROS）的生产，并增加硫氧还蛋白相互作用蛋白（TXNIP）的表达。此外，紫杉醇和香菇多糖的联合处理增强了TXNIP-NLRP 3的相互作用，并激活了NLRP 3炎性体，从而增加了IL-1β的水平，并诱导了细胞凋亡。此外，紫杉醇和香菇多糖联合应用可激活凋亡信号调节激酶1（ASK 1）/p38丝裂原活化蛋白激酶（MAPK）信号，促进细胞凋亡。紫杉醇和香菇多糖联合处理A549细胞，通过诱导ROS产生，激活NLRP 3炎性小体和ASK 1/p38 MAPK信号通路，发挥协同凋亡作用。
Paclitaxel is generally used to treat cancers in clinic as an inhibitor of cell division. However, the acquired resistance in tumours limits its clinical efficacy. Therefore, the aim of this study was to detect whether co-treatment with lentinan enhanced the anti-cancer effects of paclitaxel in A549 cells. We found that the combination of paclitaxel and lentinan resulted in a significantly stronger inhibition on A549 cell proliferation than paclitaxel treatment alone. Co-treatment with paclitaxel and lentinan enhanced cell apoptosis rate by inducing caspase-3 activation. Furthermore, co-treatment with paclitaxel and lentinan significantly triggered reactive oxygen species (ROS) production, and increased thioredoxin-interacting protein (TXNIP) expression. Moreover, co-treatment with paclitaxel and lentinan enhanced TXNIP-NLRP3 interaction, and activated NLRP3 inflammasome whereat interleukin-1β levels were increased and cell apoptosis was induced. In addition, combination of paclitaxel and lentinan could activate apoptosis signal regulating kinase-1 (ASK1)/p38 mitogen-activated protein kinase (MAPK) signal which also contributed to cell apoptosis. Taken together, co-treatment with paclitaxel and lentinan exerts synergistic apoptotic effects in A549 cells through inducing ROS production, and activating NLRP3 inflammasome and ASK1/p38 MAPK signal pathway.