REG3A promotes proliferation and DDP resistance of ovarian cancer cells by activating the PI3K/Akt signaling pathway

Abstract

AbstractThis study explored the effect of Regenerating Islet‐Derived 3‐Alpha (REG3A) on ovarian cancer (OC) progression. REG3A expression was scrutinized in clinical tissues of 97 OC cases by quantitative real‐time polymerase chain reaction (qRT‐PCR). REG3A expression in OC cells and cisplatin (DDP) resistance OC cells was regulated by transfection. LY294002 (10 μM, inhibitor of the PI3K/Akt signaling pathway) was used to treat OC cells and DDP resistance OC cells. Cell counting kit‐8 and methyl‐thiazolyl‐tetrazolium assays were applied for proliferation and DDP resistance detection. Flow cytometry was utilized for cell cycle and apoptosis analysis. The effect of REG3A on the OC cell in vivo growth was researched by establishing xenograft tumor model via using nude mice using nude mice. The expression of genes in clinical samples, cells and xenograft tumor tissues was investigated by qRT‐PCR, Western blot and immunohistochemistry. As a result, REG3A was over‐expressed in OC patients and cells, associating with dismal prognosis of patients. REG3A knockdown repressed proliferation, DDP resistance, induced cell cycle arrest and apoptosis of OC cells, and reduced the expression MDR‐1, Cyclin D1, Cleaved caspase 3 proteins and the PI3K/Akt signaling pathway activity in OC cells. LY294002 treatment abrogated the promotion effect of REG3A on OC cell proliferation, apoptosis inhibition and DDP resistance. REG3A knockdown suppressed the in vivo growth of OC cells. Thus, REG3A promoted proliferation and DDP resistance of OC cells by activating the PI3K/Akt signaling pathway. REG3A might be a promising target for the clinical treatment of OC.