PSAT1 Upregulation Contributes to Cell Growth and Cisplatin Resistance in Cervical Cancer Cells via Regulating PI3K/AKT Signaling Pathway

摘要

Standard therapy strategies for cervical cancer (CC) typically are centered on cisplatin (DDP)-based chemotherapy, while the effects of PSAT1 on cisplatin resistance in CC have not been elucidated. Cisplatin-resistant CC cell line of SiHa (SiHa-R) was established and short hairpin RNA (shRNA) targeting PSAT1 was generated to evaluate the effect of PSAT1 knockdown on CC progression. Cell viability and apoptosis were examined by using CCK-8 and flow cytometry assays. The protein levels of p-Akt, t-Akt, PCNA, cleaved caspase-3, P-glycoprotein (P-gp), and multidrug resistance related protein (MRP)-l were assessed by western blotting. Cisplatin-resistant CC cells (SiHa-R) exhibited higher expression level of PSATl rather than parental SiHa cells. PSATl knockdown lowered the IC_50 of cisplatin, inhibited the colony formation numbers, and facilitated the apoptosis ability in SiHa-R cells. PSATl knockdown also suppressed the protein levels of phospho-Akt, proteins involved in proliferation (PCNA) and drug resistance (P-gp and MRP-1), increased apoptosis related protein (cleaved caspase-3), while the PI3K/Akt agonist, 740 Y-P, markedly reversed these above effects. Inhibition of PSATl reduced cisplatin resistance in SiHa-R cells through suppressing proliferation and inducing apoptosis by blocking PI3K/Akt signaling pathway. PSATl may be a potential therapeutic target to reverse chemoresistance in cisplatin-resistant CC.