Oridonin Improves the Sensitivity of Multiple Myeloma Cells to Bortezomib through the PTEN/PI3K/Akt Pathway

Bortezomib is an effective drug for the treatment of multiple myelomas. However, its long-term effectiveness is limited by the development of drug resistance. Oridonin, a natural diterpenoid purified from Rabdosia rubescens, has the potential to diminish resistance to bortezomib. To examine the mechanism underlying the diminution of bortezomib-resistance in multiple myeloma by oridonin, we have created a bortezomib-resistant cell line of multiple myeloma cells (RPMI-8226R). Using MTT assay, apoptosis assays and western blot analysis, we evaluated and compared the effects of oridonin on the cell viability, proliferation, apoptosis, and protein expression levels in bortezomib-resistant (RPMI-8226R) and bortezomib-sensitive (RPMI-8226) myeloma cells. The results show that oridonin sensitized multiple myeloma cells leading to increased apoptosis rate via regulating the PTEN/PI3K/AKT pathway. Furthermore, oridonin activated the expression of PTEN, which is a negative regulator of the PI3K/AKT pathway, while inhibitinged the expression of p-Akt. These results demonstrated that oridonin might be a useful natural compound in bortezomib-resistant multiple myeloma treatment.