Oridonin induces apoptosis and reverses drug resistance in cisplatin resistant human gastric cancer cells.

ABSTRACT

Gastric cancer is the third most frequent cause of cancer-associated mortality and almost all patients who respond initially to cisplatin (DDP) later develop drug resistance, indicating multi-drug resistance (MDR) is an essential aspect of the failure of treatment. The natural diterpenoid component Oridonin (Ori) has exhibited efficient inhibition in several types of human cancer. However, the effect and potential mechanism of Ori-reversed MDR in human gastric cancer has not been fully elucidated. In the present study, it was found that Ori significantly suppressed DDP-resistant human SGC7901/DDP cell proliferation, growth and colony formation, causing increased caspase-dependent apoptosis, decreased expression of P-glycoprotein (P-gp), encoded by the MDR gene, multi-drug resistance-associated protein (MRP1), and cyclin D1. SGC7901/DDP cells were cultured with different groups of drugs (Ori, DDP alone, or the combination of Ori and DDP). The drug sensitivity, cell apoptosis and effects on MDR were detected by MTT assay and western blot analysis. The results revealed that Ori is able to reverse the DDP resistance and has a clear synergistic effect with DDP in SGC7901/DDP cells by decreasing the levels of P-gp, MRP1, cyclin D1 and cancerous inhibitor of protein phosphatase 2A. Thus, Ori may be a novel effective candidate to treat DDP-resistant human gastric cancer cells.