SHCBP1 Promotes Cisplatin Resistance of Ovarian Cancer Through AKT/mTOR/Autophagy Pathway

Abstract

Abstract Ovarian cancercaused the highest cancer-related mortality among female reproductive system malignancies. Platinum-based chemotherapy is still the footstone of the chemotherapy for ovarian cancer. However, the molecular mechanisms underlying cisplatin insensitivity and resistance remain unclear. SHC SH2 domain-binding protein 1 (SHCBP1) plays critical roles in the progression and drug resistance of different types of cancer. However, the biological function of SHCBP1 in ovarian cancer progression and cisplatin resistance remains obscure. In this study, we found that SHCBP1 was up-regulated in ovarian cancer and the up-regulated SHCBP1 has growth-promoting effect on ovarian cancer cells. Furthermore, SHCBP1silencing sensitize ovarian cancer cells to CDDP. Mechanism analysis revealed that SHCBP1 activated the Akt/mTOR pathway and further inhibited autophagy in ovarian cancer cells. Meanwhile, Autophagy inhibitors combined with SHCBP1 knockdown enhances CDDP sensitivity. In addition, SHCBP1 inhibition restrained the proliferation of tumorsand increased the cisplatin sensitivity in vivo. These findings suggested that up-regulated SHCBP1 promoted the proliferation and CDDP resistance of ovarian cancer.The combination of SHCBP1 inhibition and cisplatin treatment might lead to substantial progress in ovarian cancer targeted therapy.