Research On The Effects Of Survivin Antisense Oligonucleotide Inhibiting The Proliferation And Inducing Apoptosis Of Colon Cancer Cell Line

Background: Tumor is one of the main reasons that causes the death of more than 6,000,000-7,000,000 people per year in the world. Colorectal cancer is one of the most common malignacies, the incidence of which has increased rapidly in China. Low rates of early diagnosis and curative resection combine to produce the depressing prognosis. Apoptosis phenomenon is a hot topic. Survivin, a novel inhibitor of apoptosis deserves more attention as a selective target for cancer therapy because it is abundantly expressed in a variety of human tumors and is undetectable in terminally differentiated adult tissue.Objective: To investigate the effects of antisense oligonucleotide (ASODN) targeting survivin on colon cancer cells HT-29 proliferation, apoptosis, and sensitivity to chemotherapeutic drugs.Methods: Antisense oligonucleotide of different concentration was used. After transfection for 6h, culured cells were harvested to carry on the next tests. Cell morphological change was observed with invert microscope. Rate of inhibition(IR) by ASODN or ASODN combining chemotherapeutic drug was determined by the colorimetric MTT cell viability/proliferation assay. Expression of survivin protein in ASODN was detected by immunohistochemical study. Apoptosis index(AI) of cells was detected by flow cytometry.Results: IR of 400nmol/LASODN was 59.51%. Compared with control group it could significiantly inhibit the proliferation and could induce coloncancer cells HT-29 apoptosis. Further more, 200nmol/L ASODN couldefficiently enhance cell's sensitivity to 5-FU or DDP. After transfection, the expression of survivin protein in HT-29 significantly decreased. AI of ASODN group was higher than those of control groups and the group of ASODN combining chemotherapeutic drug was more significiant.Conclusions: Survivin ASODN can inhibit the proliferation and induce cell apoptosis of colon cancer cells HT-29, and after transfection the expression of survivn may decrease. These findings indicate survivin ASODN may be a new target of treatment to colorectal cancer.