| Objectives Malignant tumors are known as "the king of all diseases" because of t heir complex pathogenesis,insidious pathogenesis,and heterogeneity of the disease.S ince the 1920 s,the use of cytotoxic drugs as a representative of the internal medici ne began to emerge,and it is still an effective internal medicine for the treatment of malignant tumors.In recent decades,targeted drugs have been developed graduall y,mainly in blocking the molecular mechanism of tumor pathogenesis and anti-angi ogenesis.Apatinib is an anti-vascular target drug independently developed in China,which can competitively bind to the ATP binding site of VEGFR2,block the casca de reaction signal and reduce angiogenesis.Apatinib has been proved to be effective in gastric cancer,lung cancer,breast cancer and other diseases,and is widely use d in clinical practice.There is obvious angiogenesis in the bone marrow of patients with multiple myeloma,and thalidomide with anti-vascular effect has become an im portant drug for the treatment of multiple myeloma.Whether apatinib has a better in hibitory effect on multiple myeloma is the main purpose of this study.To investiga te the inhibitory effects of apatinib on human Multiple myeloma RPMI8226 cells and the regulation of VEGFR2/STAT3 signal pathway,exploring the possible mechani sm.Methods MTS assay was used to assess the cytotoxicity of apatinib in RPMI8226 cells.The apoptosis and cell cycle changes of the cells in response to apatinib tre atment were analyzed by flow cytometry.The expressions of Bax and Bcl-2 were a ssayed by Western Blot.The effect of Apatinib on the expressions of p-VEGFR2 an-d p-STAT3 in RPMI8226 cells were evaluated using Western Blot.Using SPSS13.0 statistical software,analysis of variance method processing data.The experimental r esults are expressed as mean±standard deviation,P<0.05 considered statistically signif icant.Use Graph Pad Prism software for drawing.Results 1 respectively 0?mol/L?10?mol/L?20?mol/L?30?mol/L?40?mol/L?60?mol/L of Apatinib intervention cells,the inhibition rate of each group was(0.00±2.30)% ?(8.44±1.87)%?(40.05±3.07)%?(69.48±0.45)%?(85.17±0.73)%?(90.36±0.55)%,Apatinib significantly inhibited the proliferation of RPMI8226 cells in vitro wit h an IC50 of 22.03±0.32?mol/L.2 respectively 5?mol/L of Apatinib intervention ce lls for 48 h,the apoptotic rate was(5.00±0.78)%,produced no significant effect o n the cell cycle(P>0.05),respectively 10?mol/L of Apatinib intervention cells,the a poptotic rate was(6.93±0.65)%,the result was statistically significant(P<0.05),resp ectively 20?mol/L of Apatinib intervention cells,the apoptotic rate was(27.23±2.15)%,the result was statistically significant(P<0.01).3 respectively 0?mol/L?5?mol/L?10?mol/L?20?mol/L of Apatinib intervention cells,the cell cycle distribution was(24.18±3.96)%?(28.43±11.18)%?(26.97±1.40)%?(19.27±8.64)% in G0/G1,was(48.53±6.77)%?(46.53±2.99)%?(52.37±3.20)%?(51.30±11.20)% in S,was(15.63±3.52)%?(7.26±5.78)%?(1.85±0.61)%?(2.21±0.57)% in G2/M,produced no significant effect on he cell cycle(P>0.05).4 Western blotting showed that Apatinib induce the expressi on of pro-apoptotic protein Bax and inhibited the expression of anti-protein Bcl-2 a fter a 48-h treatment.The expressions of p-VEGFR2 and p-STAT3 decreased in RP MI8226 cells,but the total protein level didn't undergo obvious changes.Conclusions Apatinib inhibits the proliferation and apoptosis of RPMI8226 cells in vitro,but produce no significant effect on the cell cycle.The modulation of VEGFR2/STAT3 signal pathway may be involved in its potential mechanism.VEGFR2/STAT3 signal pathway may be involved in its potential mechanism.Figure5;Table5;Reference 83... |
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