Chemosensitivity On Combination Of Decitabine And Cisplatin For Colorectal Cancer

Part I The influence of combination of decitabine and chemotherapy for different cancersObjective To evaluate the chemosensitivity of different cancers to combination of decitabine and chemotherapy and investigate the proliferation and cell pathway of them.Material and methods 14 cancer cell lines were cultured and separated in control group and decitabine group. The inhibition of cancer cells was evaluated successfully using the CCK8 assay after treatments of cisplatin or paclitaxel or 5-fluorouracil and after treatments of different pathway inhibitions.Results In all 14 cell lines, colorectal cancers were in general more effective than others with cisplatin treatment. Results between two groups has statistical significance (p<0.05). Compared to other cancer cells, decitabine and cisplatin for lung cancer cells and SKOV3 were related with a better inhibition. BAY 11-7802 was significant (p<0.05) and we inferred that NF-κB pathway was the main pathway on chemosensitivity.Conclusion These data demonstrate that pre-treatment with decitabine for colorectal cancer cells will increase the chemotherapy of cisplatin. The pharmacological mechanism may be activating NF-κB pathway and induce apoptosis of it.Part II Establish xenograft model in nude mice and supervise the effective after combined chemotherapyObjective To investigate whether decitabine is therapeutically efficacious in combination with cisplatin in vitro.material and methods Xenograft model in nude mice was established by subcutaneous inoculation of 5 x 106 CT26 cells. When the diameters reached about 1.0cm, we separated mice into four groups of control group, decitabine group, cisplatin group and DAC+DDP group. The tumors size was measured every three days from the day of injection. Tumor volumes were calculated using the equation V (in mm3)=A×B2/2. A is the largest diameter and B is the perpendicular diameter. Overall survival was assessed using Kaplan-Meier curves.Results Combination of decitabine and cisplatin was associated with longer survival and lower proliferation. The median overall survival was about 60 days with statistics significant(p<0.05)Conclusion Mice treated with decitabine showed significantly reduced tumor volumes compare with those of others.These findings indicate that decitabine can enhance sensitivity to cisplatin treatment in colorectal cancer.