Combination Treatment By Arsenic Trioxide And Paclitaxel Induce Apoptosis In Mouse Colon Cancer CT26Cells And Its Mechanism

Objective:To study the effect of arsenic trioxide (As2O3) on paclitaxel(PTX) to induce apoptosis in mouse colon cancer CT26cells and itsmechanism. To Provide theoretical basis for colon cancer chemotherapy,Thusproviding a new method and idea for the clinical management of colon cancer.Methods:To cultivate colon cancer cells (CT26) in vitro.To dilute As2O3and PTX in proportion, finally to bring As2O3concentration of0,1.0,2.0,4.0,8.0μmol/L, and to bring PTX concentration of0,0.1,0.2,0.4, and0.8μmol/L,Cells were treated with different concentrations of As2O3, Cell growthrate was detected by MTT assay. To observate Cell morphology changes underinverted phase contrast microscope,after Cells were treated with differentconcentrations and different time.After cell is inoculated in6Orifice plate in thelogarithmic phase and is cultivated for24h,cells were treated with As2O3at30%effective dose cooperative with different concentrations of PTX to find outthe most effective combination dose on cell growth inhibition. Apoptosis rateand cell cycle of each group were assessed by flow cytometer. Western Blotanalysis was used to detected the protein expression of Bax, Bcl-2and PARP of cells.Results:With different concentrations of As2O3to process colon cancercells in mice (CT26) for72h,to detect cell proliferation by MTTmethod.As2O3or PTX alone inhibit CT26cell growth in a dose dependentmanner. Combination treatment of As2O3at2μmol/L and PTX at0.04μmol/Lshowed the beat effect in cell growth inhibition, as well as induced increasedlevel in apoptosis rate of cells compared with single treatment.Mechanismcould be effectively inhibited or blocked the cell proliferation and survivalfactors.As2O3single-agent can make the cell cycle arrest in G1phase andPTX single-agent block cell in G2/M phase（40.22±3.71%，controlgroup:4.45±1.82%）.After the combination, S period significantly decreased to17.88%(control group60.20±3.85%)，The cell cycle is mainly blocked in G1phase and G2/M phase。Combination action of As2O3and PTX significantlyup-regulated apoptosis rate and Bax and cleavage PARP, down-regulated Bcl-2expression compared with As2O3and PTX alone(all P＜0.05).Conclusion:Combination treatment of As2O3and PTX inhibit cell growthand induced apoptosis through up-regulation Bax/Bcl-2and cleavage PARP.