| The breast cancer is a common malignant tumor which threaten to the health of women, every year there are new 1.2 million women that suffered from breast cancer all around the world, and five hundreds thousand women died of breast cancer. China is a developing country, but the morbidity of breast cancer is similar to developed countries, and there is a tendency of rise every year. Some data have demonstrated the morbidity of breast cancer have increased 37.6% in the recent two decades, the annual increasing rate have reached 2.3% averagely. By 2000, the morbidity of breast cancer has reached 28.8/100 000, which was the first one among all the women tumors. Modern management of breast cancer is integrated treatments that major in surgical treatment, and endocrine therapy is an important part of integrated treatment. Tamoxifen has been applied in clinical practice for over thirty years as a first line drug in endocrine therapy for breast cancer. Traditional opinion on the mechanism of TAM is believed to be combined to specific receptor site which competitive with estradiol, and form an anti-estrogen complex with low activity, downregulate the activities of cancer cell, arrest breast cancer cell in G1 phase, decrease the portion of S phase cells. Recently, some studies have demonstrated that TAM could inhibit the growth of breast cancer cells by apoptosis. Survivin is a novel anti-apoptotic factor found by Altieri et al in 1997, and it is the smallest member of IAP (inhibitor of apoptosis) family. Survivin was observed to express in fetal tissues and most common human cancers, including carcinomas of lung, stomach, colon, breast, and prostate as well as high-grade non-Hodgkin's lymphomas, whereas no survivin transcripts were detected in normal, terminally differentiated adult tissues (except thymus gland and genital gland). Experimental data suggested that survivin functions similarly to other human IAPs, binding to active caspase-3 and -7 by a manner of BIR dependant, prevent apoptosis by inhibiting the activities of caspase-3 and -7. Because of the selective expression of survivin in cancer tissues, it has become the hot spot in many studies which focused on cancer treatment. Researches have demonstrated that tumor cells became more sensitive to chemotherapy after the expression of survivin was inhibited; on the other hand, after the survivin cDNA were transfected into tumor cells, these cells become resistant to chemotherapy. But until now, there are no reports on the relationship between survivin and apoptosis of breast cancer cells induced by TAM, and whether the sensitivity of breast cancer cells to TAM are increased by inhibiting the expression of survivin.The purpose of the research was to study the relationship between the expression of survivin and the apoptosis of breast cancer cells induced by TAM. In this experiment, we have observed the apoptosis of MCF-7 breast cancer cells induced by TAM, the roles of TAM on the changes of survivin gene, and the changes of apoptotic rate of MCF-7 cells after treated by the TAM which combined with antisense oligonucleotide targeting survivin mRNA. Our results have revealed that the apoptosis of MCF-7 cells induced by TAM were related to the downregulation of survivin expression, and antisense oligonucleotide targeting survivin mRNA could make MCF-7 cells more sensitive to TAM. â… . The role of TAM on survivin gene and its mechanismMCF-7 cell line was treated by various concentrations of TAM, and after various period of time, samples were extracted. The effects of TAM on the changes of apoptotic rate and distribution of cell cycle of MCF-7 cells were examined by flow cytometry; the positive rate of survivin mRNA and expression of survivin protein were confirmed by hybridization in situ and western blotting; the expression of caspase-3 protein and the activities of caspase-3 were evaluated by immune histochemistry and colorimetry. The results have demonstrated:(1) The apoptosis of MCF-7 cells induced by TAM was significantly time-dependa...
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