DST regulates cisplatin resistance in colorectal cancer via PI3K/Akt pathway.

Abstract

Dystonin (DST), a potential tumor suppressor gene, plays a crucial role in regulating cancer cell proliferation and resistance to chemotherapy. However, DST's specific role in colorectal cancer (CRC) has not been thoroughly investigated, and this study aims to elucidate its molecular role in modulating cisplatin (DDP) resistance in CRC. DST expression was analyzed in CRC tumors, DDP-resistant CRC tissues, paracancer tissues, and normal tissues. Lentiviral overexpression and shRNA knockdown were conducted in advanced CRC and DDP-resistant cell lines to assess cell viability, apoptosis, invasion, migration, proliferation, and angiogenesis. Xenograft mouse models studied DST's impact on CRC tumor growth and DDP resistance in vivo. DST expression was significantly reduced in CRC tumor and DDP-resistant CRC tissues compared to paracancer and normal tissues (P < .001). Upregulating DST inhibited CRC and DDP-resistant cell viability, proliferation, invasion, and migration while promoting apoptosis. DST overexpression also reduced angiogenesis and attenuated DDP-induced cytotoxicity in CRC cells. Mechanistically, DST upregulation suppressed DDP resistance in CRC cells via the PI3K/Akt signaling pathway. DST upregulation reduced CRC tumor growth and mitigated DDP resistance, in vivo. DST plays a crucial role in limiting CRC progression and overcoming DDP resistance, suggesting potential for targeted CRC therapies.