RESUMO
Objective To elucidate the inhibitory effect of 131I-fulvestrant on the growth of human breast cancer cells and the effect on the important organs.Methods MTT assay was used to clarify the difference in killing effects of the 131I-fulvestranton on MCF-7 cells and MDA-MB-231 cells.Breast cancer MCF-7 cell xenografts in nude mice was establishied,and two different administration methods of the 131I-fulvestrant in the MCF-7 cell to nude mice were given respectively.Organs and tumours of nude mice were observed.Results MTT assay demonstrated that 131I-fulvestrant had similar cytotoxicity against MCF-7 cells and MDA-MB-231 cells,and the former was slightly stronger.Transient contact experiments showed that 131I-fulvestrant could play a tumor suppressor effect on MCF-7 cells continually,but MDA-MB-231 cells wasn't.After the injection of 131I-fulvestrant via caudal vein,the radioactivity concentration on tumor site accounted for (4.33 ± 0.28)％ of the total injection,and the volume of the tumor reduced before gradually increasing again.Radioactivity in the blood accounted for (20.76 ± 2.54)％ of the total injection.Qrgans like liver and kidney also showed radioaction distribution.Its distribution was accorded with the distribution of estrogen receptor.Local injection of 131I-fulvestrant got powerful killing effect on the tumor,and the distribution of the radioaction was mainly confined within the tumor.Conclusion 131I-fulvestrant has a good inhibitory effect on MCF-7 breast cancer cells,which is a superposition of radiotherapy and endocrine therapy,and it is controllable on the general condition and important organs of nude mice.
RESUMO
Cancer chemotherapy remains one of the preferred therapeutic modalities against malignancies despite its damaging side effects. An expected outcome while utilizing chemotherapy is apoptosis induction. This is mainly regulated by a group of proteins known as the Bcl-2 family, usually found within the endoplasmic reticulum or the mitochondria. Recently, these proteins have been located in other sites and non-canonic functions have been unraveled. Bik is a pro-apoptotic protein, which becomes deregulated in cancer, and as apoptosis is associated with oxidative stress generation, our objective was to determine the subcellular localization of Bik either after a direct oxidative insult due to H2 O2 , or indirectly by cisplatin, an antineoplastic agent. Experiments were performed in two human transformed mammary gland cell lines MDA-MB-231 and MCF-7, and one non-tumorigenic epithelial cell line MCF-10A. Our results showed that in MCF-7, Bik is localized within the cytosol and that after oxidative stress treatment it translocates into the nucleus. However, in MDA-MB-231, Bik localizes in the nucleus and translocates to the cytosol. In MCF10A Bik did not change its cellular site after either treatment. Interestingly, MCF10A were more resistant to cisplatin than transformed cell lines. This is the first report showing that Bik is located in different cellular compartments depending on the cancer stage, and it has the ability to change its subcellular localization in response to oxidative stress. This is associated with increased sensitivity when exposed to toxic agents, thus rendering novel opportunities to study new therapeutic targets allowing the development of more active and less harmful agents.
