Abstract

Epidermal growth factor receptor (EGFR) signalling and the interleukin-6 (IL-6)/signal transducer and activator of transcription 3 (STAT3) are aberrantly activated in ovarian cancer. However, inhibition of EGFR signalling in ovarian cancer patients resulted in a disappointing clinical benefit. In this study, we found that EGFR could activate IL-6-STAT3 pathway in ovarian cancer cells. However, we also demonstrated that EGFR knockdown could increase STAT3 phosphorylation in HO8910 and OVCAR-3 ovarian cancer cells. Interestingly, we further demonstrated that the non-coding RNA miR-146b could simultaneously block both the EGFR and IL-6-STAT3 pathways. Finally, our data demonstrated that miR-146b overexpression resulted in a greater suppression of cell migration than STAT3 pathway inhibition alone.These results suggest a complex and heterogeneous role of EGFR in ovarian cancer. Combined blockade of EGFR and IL-6-STAT3 pathways by miR-146b might be a strategy for improving the clinical benefit of targeting the EGFR pathway in ovarian cancer patients in the future.

摘要

表皮生长因子受体 (EGFR) 信号传导和白细胞介素 6 (IL-6)/信号转导和转录激活因子 3 (STAT3) 在卵巢癌中异常激活。然而，抑制卵巢癌患者的 EGFR 信号导致了令人失望的临床益处。在本研究中，我们发现EGFR可以激活卵巢癌细胞中的IL-6-STAT3通路。然而，我们还证明了 EGFR 敲低可以增加 HO8910 和 OVCAR-3 卵巢癌细胞中的 STAT3 磷酸化。有趣的是，我们进一步证明了非编码 RNA miR-146b 可以同时阻断 EGFR 和 IL-6-STAT3 通路。最后，我们的数据表明，与单独的 STAT3 通路抑制相比，miR-146b 过表达对细胞迁移的抑制更大。这些结果表明 EGFR 在卵巢癌中的复杂和异质作用。miR-146b 联合阻断 EGFR 和 IL-6-STAT3 通路可能是未来提高靶向 EGFR 通路在卵巢癌患者中的临床获益的一种策略。