Inhibitory Effect Of Taxol Derivative TM-2 On Tumor Proliferation In Vitro And Its Mechanism

Objective:Investigate the inhibitory effect of taxol derivative TM-2 on the proliferation of tumor cells and its possible mechanism.Methods:MTT was used to detect cell proliferation inhibition in vitro cultured cells.GraphPad 5 Prism was used to calculate IC50,Annexin V-FITC/PI double staining and flow cytometry,Observed and analyzed the apoptosis rate.Mitochondrial membrane potential,and Western Blot were used to detect the effect of TM-2 on the expression of apoptosis related proteins.Results:(1)Taxol derivative TM-2 can inhibit the proliferation of tumor cells,the IC50 of human prostate cancer(PC-3)cells and human ovarian cancer cells(SK-OV-3,A2780),human cervical carcinoma(HeLa)cells and human breast cancer(MCF-7)cells,human colorectal cancer(HCT-116)cells and human hepatoma(HepG2)cells,human pancreatic cancer(BxPC-3)cells,human lung adenocarcinoma(A549)cells were 0.0030 uM,0.0057 uM,0.0028 uM,0.0126 uM,0.0023 uM,0.0036 uM,0.0159 uM,0.0132 uM and 0.0098 uM(2)The mitochondrial membrane potential results showed that with the increase of TM-2 concentration,mitochondrial membrane of tumor cells were 91.3%,87.48%,83.11%,77.97%;(3)The double staining results showed that with the increase of TM-2 concentration,the apoptotic cell number were 6.29%,20.45%,40.4% and 55.8%;(4)The Western Blot results showed that with the increase of TM-2 concentration,can obviously promote the degradation of Caspase-3,Caspase-8 and caspase-9 zymogen.with the dose increased,the degradation of Caspase-3 substrate PARP is more and more obvious.The expression of Bax protein was up-regulated,the expression of Bcl-2 protein was down regulated,and the ratio of Bax /Bcl-2 was increased.Conclusion:TM-2 can inhibit a variety of human tumor cell proliferation in vitro,the mechanism may be related to the activation of the mitochondrial and death receptor pathways,up regulation of the expression of Bax protein,and down the Bcl-2 protein expression,decreased mitochondrial membrane potential,activation of Caspase-3 cleaveage apoptosis.