Effects Of STI571 Alone And In Combination With As₂O₃ On Proliferation Of The Multiple Myeloma Cell

Objective To explore the effects of STI571 alone and in combination with As₂O₃ on mouse multiple myeloma(MM) cell lines SP2/0 and its possible mechanisms.Methods: The object was divided into nine groups :control, 1.0μmol/L As₂O₃,2.0μmol/L As₂O₃,10.0μmol/L STI571,25.0μmol/L STI571,and the combinated group 1.0μmol/L+ 10.0μmol/L,1.0μmol/L+25.0μmol/L,2.0μmol/L+10.0μmol/L,2.0μmol/L+25.0μmol/L .The time was divided into three levels:24 o'clock ,48 o'clock, 72 o'clock. Western blot technique was used to detect the expression of P₁₆ protein in SP2/0 cell;the DNA content of MM cell line SP2/0 was analysed by flow cytometry after exposure to As₂O₃ and/or STI571;the activity of cell was detected with MTT method.Results The Western blot result show the expression of P₁₆ protein has significant difference in the different density of As₂O₃ or STI571 groups in the SP2/0 cell. There is not the expression of P₁₆ protein in the control group.There are interaction between As₂O₃ and STI571 and time. The positive expression of P₁₆ protein was the highest in As₂O₃1.0μmol/L and STI571 25.0μmol/L and 72 o'clock group.DNA flow cytometry analysis show that As₂O₃ and /or STI571 induced most of SP2/0 cells arrest at G1 phase and decrease significantly in S phase. MTT result show the growth of SP2/0 cells was inhibited and the viability of SP2/0 was decreased in time- and dose-dependent manner after exposure to As₂O₃ and /or STI571.?Conclusion:One of the pharmacological mechanisms of STI571 combination with As₂O₃ is to activate or upregulate the expression of cyclin dependent kinase inhibitors (CDKIs) protein P₁₆ and consequently affect cell proliferation cycle.