The overexpression of EGFR and/or ErbB2 occurs frequently in ovarian cancers and is associated with poor prognosis. The purpose of this study was to examine the anticancer effects and molecular mechanisms of berberine on human ovarian cancer cells with different levels of EGFR and/or ErbB2. We found that berberine reduced the motility and invasiveness of ovarian cancer cells. Berberine depleted both EGFR and ErbB2 in ovarian cancer cells. Furthermore, berberine suppressed the activation of the EGFR and ErbB2 downstream targets cyclin D1, MMPs, and VEGF by down-regulating the EGFR-ErbB2/PI3K/Akt signaling pathway. The berberine-mediated inhibition of MMP-2 and MMP-9 activity could be rescued by co-treatment with EGF. Finally, we demonstrated that berberine induced ErbB2 depletion through ubiquitin-mediated proteasome degradation. In conclusion, the suppressive effects of berberine on the ovarian cancer cells that differ in the expression of EGFR and ErbB2 may be mediated by the dual depletion of EGFR and/or ErbB2.

中文翻译：

---

小檗碱对EGFR和ErbB2的双重下调有助于抑制人卵巢癌细胞的迁移和侵袭

EGFR 和/或 ErbB2 的过度表达在卵巢癌中经常发生，并且与预后不良有关。本研究的目的是检查小檗碱对具有不同水平 EGFR 和/或 ErbB2 的人卵巢癌细胞的抗癌作用和分子机制。我们发现小檗碱降低了卵巢癌细胞的运动性和侵袭性。小檗碱消耗了卵巢癌细胞中的 EGFR 和 ErbB2。此外，小檗碱通过下调 EGFR-ErbB2/PI3K/Akt 信号通路抑制 EGFR 和 ErbB2 下游靶标细胞周期蛋白 D1、MMP 和 VEGF 的激活。小檗碱介导的 MMP-2 和 MMP-9 活性抑制可以通过与 EGF 共同处理来挽救。最后，我们证明小檗碱通过泛素介导的蛋白酶体降解诱导 ErbB2 耗竭。综上所述，