Tubeimoside â…  Enhanced Chemosensitivity Of A2780/DDP To Cisplatin

Objective: To study how to use TBMS1 to increase the promotion of cisplatin for chemosensitivity of ovarian cancer A2780/DDP cells, and provide comprehensive treatment for clinical guidance based experimental dataMethods: MTT was used test the IC₅₀ of cisplatin and TBMS1 for A2780/DDP cells, respectively. The growth of cells colonies was detected by cell cloning experiment and the intracellular DNA damage detected by electrophoresis. Furthermore, the apoptosis, proliferation of cells and intracellular release concentration of Ca²⁺ were detected by flow cytometer.Results: TBMS1 and cisplatin all can promote cell apoptosis by MTT.The cell cloning experiment indicate that the cell colonies are decreased apparently after the TBMS1 (6μmol/L) combination with cisplatin (8μmol/L). The intracellular DNA damage was increased significantly by the increase of TBMS1. Compared with the control group (4.73±2.1)%, the apoptosis rate of drug combination was increased to (7.59±1.6)% (P< 0.05). The TBMS1 combination with cisplatin treatment cell A2780/DDP shows that proliferation of cells was inhibited, the supress rate was (22.79±0.2)% compared with the control group (13.56±1.3)%. There was statistical significance (P< 0.01); Moreover, the intracellular release concentration of Ca²⁺ was increased to (12.81±3.2)%, compared with the control group (P< 0.01).Conclusion: The combination of TBMS1 and cisplatin can promote the apoptosis of ovarian cancer cell A2780/DDP. This may be related to the increase of sensitivity to cisplatin of A2780/DDP by TBMS1.Objective: To study the possible mechanism of sensibilization of ovarian cancer A2780/DDP cells for cisplatin increased by TBMS1.Methods: Western Blotting analyzes of the expression of Bcl-2, Bax, P38, ERK1/2 and GST-Ï€; RT-PCR analyzes the GST-Ï€of the expressions level of mRNA. Moreover, we used the inhibitor of P38 (SB203580) or ERK1/2 (PD98059) to pretreat the A2780/DDP cells for 1 hour, then the protein expression of Bcl-2 and Bax was clearly detected by Western Blotting.Results: Compared with the control group, the expression of Bcl-2 of the combination group ( 6μmol/LDDP + 8μmol/L TBMS1) was decreased (88.4±3.9)%(P< 0.01), however, the expression of Bax was increased (53.2±5.2)%(P< 0.05).P-P38, one of the MAPK signal channels regarding to tumor apoptosis, was up-regulated (P<0.01). Whileas, P-ERK1/2 was down-regulated. The protein expression of Bcl-2 and Bax was both inhabited in the SB203580 group and PD98059 group. The expression of multidrug-resistant protein GST-Ï€and mRNA were decreased with the drug combination of cisplatin, and the difference from control group has statistical significance. P38 and that ERK1/2 signaling pathways involved in TBMS1 enhancing A2780 / DDP cells cisplatin sensitivity of this process.Conclusion: The sensibilization of ovarian cancer A2780/DDP cells for cisplatin increased by TBMS1 may be related to the up-regulation of P38 and the down-regulation of ERK. The experimental result provides a good experimental basis about the clinic of traditional combination when it is very difficult to solve the problem of cisplatin resistance.