Effect Of Curcumin On The Proliferation And Cytokine Secretion Of Bone Marrow Stromal Cells Of Patients With Multiple Myeloma

So far, multiple myeloma remains to be an uncurable disease. There are some patients may presentrecurrence, resistance or intolerance for further chemotherapy after receiving routine or high-dosechemotherapy, and little improvement of efficacy can be achieved. Therefore, the biological and molecularbasis of multiple myeloma should be studied to discover new chemotherapeutic drugs and pioneer moreeffective therapeutic scheme for overcoming resistance of myeloma cells, pursuiting for more satisfactorycurative effect. Interleukin-6(IL-6) and vascular endothelial growth factor (VEGF) influence the proliferationand migration of multiple myeloma cells and their secretion is affected by the interaction between myelomacells and bone marrow stromal cells. More and more molecular targets are discovered in research ofpathophysiology of MM and the drugs acting on the targeting sites are becoming more improtant..This experiment was designed to study the effect of curcumin on the proliferation and cytokine secretionof bone marrow stromal cells from the patients with multiple myeloma, including the laboratory part and theclinical part.PartⅠThe laboratory part【Objective】: To explore the effect of curcumin on growth and secretion of interleukin-6(IL-6) and vascularendothelial growth factor (VEGF) of bone marrow stroma cells (BMSCs) from the patients with multiplemyeloma (MM).【Method】: Specimens of bone marrow aspirating from MM patients were used to establish BMSC cultures.BMSCs and human MM cell line U266were cultured together or alone in the absence or presence of curcuminat various concentrations (1-40.0μmol/L). Cell growth inhibition was assessed by MTT assay, cytokines inthe culture supernatants were measured with ELISA. 【Result】: Curcumin could inhibit the growth of U266, with fifty percent growth inhibition (IC50) for48hours at2.3mol/L. However, curcumin had no effect on the growth of BMSCs. High levels of IL-6and VEGFhad been found in the culture supernatants of BMSCs from MM patients. Cytokine prodution of BMSCstreated with curcumin significantly decreased as compared with controls (P <0.05). Excitingly, even theincreased cytokine production triggered by adhesion of MM cell and BMSCs was also inhibited by curcumin.【Conclusion】: After the treatment of appropriate concentrations of curcumin, the levels of IL-6, VEGF canbe significantly inhibited, but does not the proliferation of MM BMSCs.Part Ⅱ The clinical partEffect of curcumin combined bortezomib, dexamethasone in thetreatment of multiple myeloma【Objective】: To evaluate the efficacy and safety of curcumin combined with bortezomib, dexamethasone inthe treatment of multiple myeloma（MM）.【Method】: Twenty patients with MM as experiment group were treated by curcumin (200mg/d p.o.)combined with bortezomib (1.3mg/m2d1、4、8、11), dexamethasone (DEX,40mg d1、4、8、11), the other20patients with MM as controlled group were just treated by bortezomib combined with DEX every3weeks.The regimen had repeated for4-6cycles.【Result】: Five patients in the experiment group had a complete remission (CR),11cases achived partialremission（PR）,2minor response and2in ineffectivity. The total effective rate was90%, which was obviouslyhigher than that of the control group,which was just80%. The adverse reactions were manageable in allpatients and there were no difference in two groups.【Conclusion】: Curcumin combined with bortezomib, dexamethasone regimen had advantages of little sidereaction, well endurity in treatment of previously untreated patients with multiple myeloma.