The Correlation Between Survivin And Cellular Apoptosis, Proliferation In Colorectal Cancer

Objective To investigate clinical significance of survivin expression in rectal carcinoma, and the relationship between survivin and pentagastrin during the process of proliferation accelerated by pentagastrin, so as to search for new genetic therapy for colorectal cancer.MethodThe apoptosis in sit rectal carcinoma were identified by the terminal deoxynucleotidy transfer mediated dUTP-biotin nick end labeling(TUNEL). Microvessel density(MVD), survivin expression in 50 cases of rectal carcinoma and in colon cancer cell line SW-480 was detected by immunohistologic staining. The liposome-mediated synthetic antisense oligonucleotides(ASODN) and sense oligonucleotides(SODN) encoding survivin were delivered to the colon cancer cell line SW-480, then the apoptotic cells were detected by flow cytometry, and the growth activity and suppressive rate of colon cancer cells were measured by methyl thiazolyl tetrazolium (MTT) methods. The expression of Survivin mRNA was detected by reverse transcription- Polymerase chain reaction. The proliferation of cancer cell line SW-480 which treated by pentagastrin, Survivin ASODN and Survivin SODN was measured by MTT methods.ResultSurvivin was expressed in 28 of 50 rectal carcinoma (56%). The correlation was found between survivin expression, cellular apoptosis and angiogenesis (P<0.05). The 5 year survival rate in the group of survivin-negative cases was significant higher than in the group of survivin-positive cases (81.34% vs 50%, P<0.05). In Cox regression analysis, survivin expression and cellular apoptosis index (AI) were indpendent risk factors for prognosis. Survivin expression was positive in colon cancer line SW-480. ASODN inhibited proliferative activity and induced apoptosis of colon cancer cells in a dose-dependent manner, at the dose of 0.33μg/μl, 0.99μg/μl, 1.98μg/μl, the apoptotic rates was (8.74±0.64)%, (23.53±2.33)%, (36.87±0.61)% respectively and the arrest rates of cellular growth reached (11.34±3.01)%, (37.72±3.71)%, (50.14±3.33)% respectively. The expression of Survivin mRNA in colon cancer cell line SW-480 treated by pentagastrin was higher than the control. The proliferation effect of pentagastrin could be inhibited by Survivin antisense ODN.ConcludeSurvivin, an inhibitor gene of apoptosis, expression abnormal correlated with apoptosis inhibition, angiogenesis and poor prognosis in rectal carcinoma. The pentagastrin could promote the expression of survivin mRNA. Its anti-apoptotic and proliferative effect on colon cancer cell was achieved through the function of survivin partly. Survivin ASODN could inhibit proliferation and induce apoptosis by inhibiting the expression of survivin in colon cancer cell line SW-480. The clinic significance of antisense gene therapy targeting Survivin shows potential application to further study.