ZIPK activates the IL-6/STAT3 signaling pathway and promotes cisplatin resistance in gastric cancer cells,FEBS Open Bio

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ZIPK activates the IL-6/STAT3 signaling pathway and promotes cisplatin resistance in gastric cancer cells
FEBS Open Bio ( IF 2.8 ) Pub Date : 2021-08-10 , DOI: 10.1002/2211-5463.13270
Haonan Fan ₁ , Qifeng Ou ₁ , Qiao Su ₂ , Guanman Li _{1,

3} , Zhijuan Deng _{1,

4} , Xiaohui Huang ₁ , Jiong Bi ₁

Affiliation

Gastric cancer is one of the most common malignant cancers globally. Chemotherapy resistance remains a major obstacle in the treatment of gastric cancer, and the molecular mechanisms underlying drug resistance are still not well understood. We previously reported that Zipper interacting protein kinase (ZIPK), also known as death-associated protein kinase3, exerts an oncogenic effect on gastric cancer via activation of Akt/NF-κB signaling and promotion of stemness. Here, we explored the roles of ZIPK in cisplatin resistance. We report that ZIPK enhances cell proliferation and invasion and reduces the antitumor activity of cisplatin in gastric cancer. In addition, our western blot data suggest that ZIPK activated the IL-6/STAT3 signaling pathway. Furthermore, ZIPK increased the expression of IL-6 and multidrug-resistance genes. Using the STAT3 inhibitor stattic to block the IL-6/STAT3 signaling pathway strongly increased the sensitivity of ZIPK-expressed cells to cisplatin. In conclusion, ZIPK may play a role in cisplatin resistance through activation of the IL-6/ STAT3 signaling pathway. Inhibition of STAT3 in gastric cancer overexpressing ZIPK might have potential to improve the efficacy of cisplatin.

中文翻译：

ZIPK激活IL-6/STAT3信号通路并促进胃癌细胞顺铂耐药

胃癌是全球最常见的恶性肿瘤之一。化疗耐药仍然是胃癌治疗的主要障碍，耐药的分子机制仍不清楚。我们之前报道过 Zipper 相互作用蛋白激酶 (ZIPK)，也称为死亡相关蛋白激酶 3，通过激活 Akt/NF-κB 信号传导和促进干性对胃癌发挥致癌作用。在这里，我们探讨了 ZIPK 在顺铂耐药中的作用。我们报道 ZIPK 增强细胞增殖和侵袭并降低顺铂在胃癌中的抗肿瘤活性。此外，我们的蛋白质印迹数据表明，ZIPK 激活了 IL-6/STAT3 信号通路。此外，ZIPK 增加了 IL-6 和多药耐药基因的表达。使用 STAT3 抑制剂 stattic 阻断 IL-6/STAT3 信号通路大大增加了 ZIPK 表达细胞对顺铂的敏感性。总之，ZIPK 可能通过激活 IL-6/STAT3 信号通路在顺铂耐药中发挥作用。在过表达 ZIPK 的胃癌中抑制 STAT3 可能有可能提高顺铂的疗效。

更新日期：2021-09-01

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