Knockdown Of Atpase Family Aaa Domain-Containing Protein 2 Inhibits The Proliferation Of Colorectal Cancer Cells In Vitro And In Vivo

ATPase family AAA domain-containing protein 2 (ATAD2) has been reported to be associated with the development of many malignant cancers. Our study firstly investigated the functional roles of ATAD2 gene in colorectal cancer (CRC) in vitro and in vivo. Here, Caco-2 and SW480 cell lines were transfected with ATAD2 short hairpin RNA (shRNA) plasmid to silence ATAD2 expression, as measured by real-time PCR and western blot. Cell proliferation and cell cycle distribution in vitro were determined by CCK-8, colony formation assay and flow cytometry. The effect of ATAD2 knockdown on tumor growth and tumor weight was evaluated in BALB/c-nude mice in vivo. Meanwhile, proliferation-related and cell cycle-related proteins were examined by real-time PCR, western blot and immunohistochemistry (IHC). Our results demonstrated that ATAD2 knockdown significantly inhibited cell proliferation and arrested cell cycle at the G1 phase. Decreased levels of c-myc, proliferating cell nuclear antigen (PCNA), Ki67, phosphorylated (p)-Akt, Akt, cyclin D1, cyclin E1 and cyclin-dependent kinase 2 (CDK2) were detected after ATAD silencing, whereas p21 expression was increased. Moreover, administration of shATAD2 plasmid significantly suppressed tumor growth and reduced tumor weight in nude mice, with the decreased levels of ATAD2, PCNA, c-myc and Ki67 in tumor tissues. The results suggest that ATAD2 may play crucial roles in CRC development. Targeting ATAD2 may be an efficient therapeutic approach in CRC treatment.