| Apoptosis is programmed cell death, a physiological phenomenon, which can clearup the unwanted or defected cells actively under the strict genic regulation of our body. It's a main mechanism to maintain normal metabolism. It can preserve the balance of individual development or adult organism through eliminate the decrepit, wounded, or latent toxicity cells. So it is considered that inhibition of apoptosis is an important mechanism during the process of tumorigenesis. There is a homeostasis between the proliferation and death of cell in normal state, the mechanism which regulate the balance keep the normal physiological function. The occurment and development of tumor were related to not the abnormal of proliferation and differentiation , but also the change of cell apoptosis gene. The turbulence of modulation mechanism will induce the the occurment of tumor. Therefore, the policy of inducing the apoptosis of tumor cell has been the emphasis of tumor therapy in recent years. Survivin has recently been identified as a novel inhibitor of apoptosis (IAP). Unlike other members of the IAP family, survivin is characterized by a unique structure that contains a single baculovirus IAP repeat and no carboxyl-terminal RING finger motif. It is expressed in many common human cancers, but itsexpression is lost or down-regulated in normal adult tissues. Survivin blocks a common downstream part of two major apoptosis, the mitochondrial pathway and the death receptor pathway, by directly inhibiting terminal effector caspase-3 and caspase-7 activity. Meanwhile, the mean apoptosis index(AI) in survivin-positive tumors significantly lower than the mean AI in survivin-negative tumors. Therefore, many scholars considered that survivin could suppress apoptosis and accelerated cell proliferation. Along with going deep into the research of survivin gene, survivin will become a new diagnosis and therapeutic target in tumor.Ovarian carcinoma is the most common cause of death among all gynecologic malignancies. The overall 5-year survival rate of patients is only about 40.9%. It heavily threaten the health of women. Nowadays, with the rapid development of molecular biology, it is generally accepted that the tumorigenesis and tumor progression are closely related to the changes of tumor cell biology. However, very little is known about the exact sequence of celluar and molecular events contributing to the development of ovarian malignancy. Many studies showed that survivin expression in tumors has been associated with increased aggressiveness and decreased patient survival in many kinds of cancer. This study was designed to explore effects and change of survivin in the apoptosis of ovarian cancer cell lines SKOV3 induced by topotecan, to investigate the mechanism of apoptosis regulation and the effect of survivin enhance the sensitivity of ovarian cancer cell lines SKOV3 in chemotherapy. Methods1. The inhibition effects of different chemotherapeutical concentration of topotecan on survivin protein and mRNA expression in ovarian carcinoma SKOV3 cells were detected by immunnohistochemistry and RT-PCR respectively.2. Cells activity was investigated by MTT assay and the effect of SVVas on cells growth was described by drawing its growth curve.3. The effect of chemotherapical drug on apoptosis was detected to observe the inhibition effects of different concentration of topotecan on survivin protein and mRNA expression in ovarian carcinoma SKOV3 cells by TUNEL.Statistical analysis: The SPSS statistical package program 11.0 was used for allanalyses. Associations between the variables were tested by X2 test, t test, one-way ANOVA and F test. Satistically significant level was considered as "alpha equals 0.05". Resultsl.Immunnohistochemistry and RT-PCR investigation showed that with the concentration of topotecan increased, the expression level of survivin protein and mRNA obviously reduced in ovarian carcinoma SKOV3 cells. The different was significanet(P<0.01).2. MTT assay showed that with the concentration and time of increased, topotecan can evidently inhibit the proliferation of ovarian carcinoma SKOV3 cells, which showed a dose-and time-dependent responses.3. The ratio of apoptosis in ovarian carcinoma SKOV3 cells which not treated by topotecan was (12.61 ± 2.32) % by TUNEL staining, but the occurrence of apoptosis in SKOV3 cells treated by topotecan were (20.87 ± 3.45)%, (25.63 ± 4.58)% and (29.47 ± 5.04)% respectively. It was significant compared with the control growp (p<0.05), which showed a dose-and time-dependent manner.Conclusion1. The expression of survivin was testd in ovarian carcinoma cell lines. It suggested that survivin is involved in tumorgenesis and tumor progression, and survivin may be a good biomarker in early diagnosis and superviseing the development of ovarian carcinoma,2. Survivin is the important factor which regulates the apoptosis of ovarian cancer cell line. An important mechanism that chemotherapy treat ovarian carcinoma is inducing cell apoptosis. It suggested that survivin may be used as a sign to estimate the curative effect and to appraise the prognosis of ovarian carcinoma.3. Topotecan obviously inhibited the SKOV3 cell growth with dose-and time-dependent ,which lead to cell apoptosis by inhibiting the expression of survivin in ovarian carcinoma ,which could inhibit cell proliferation in vitro.4. Topotecan can effectively induce apoptosis in SKOV3 cells and the inhibition of survivin gene expression may play a critical role in the apoptosis ofovarian cancer cells induced by topotecan, by which a new approach for the treatmentof ovarian cancer could be investigated.
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