| Breast cancer is one of the world’s highest morbidity and mortality tumor infemales. According to statistics, breast cancer is also one of the most commonmalignancies in China. The morbidity of this disease is increase and its incidencetrends to become younger in average age. The high estrogen level in the blood or localmaybe is one of the major reasons of the most patients with breast cancer and itsrecurrence. The traditional endocrine theory includes the endocrine, paracrine andexocrine ways. The discovery of cell biology and molecularbiology opens up a theoryfor studying endocrine function and offers a new concept, the intracrine, which is firstnamed by Labrie, etc. The theory here is that the activity hormone synthesis inside thecells and direct effects on their own but not secreted to the outside of the cells or theblood. Compared to traditional endocrine mechanism, the sex hormones will notmetabolism or break down in the systemic circulation in the process of intracrine andit play a key role in the hormone-dependent tumors. It is difficult to determine directlythe hormones because of the metabolic and endocrine hormone is an intracellularprocess. The activity and the amount of the key enzyme could substitute formeasurement the cell intracrine.In postmenopausal women, the ovaries stop produce hormones, the production ofactivated sex hormone (17beta-estradiol) mainly depends on a group reduced17beta-hydroxysteroid dehydrogenases. The enzymes include17beta-hydroxysteroiddehydrogenases type1,17beta-hydroxysteroid dehydrogenases type5,17beta-hydroxysteroid dehydrogenases type7and17beta-hydroxysteroiddehydrogenases type12.17Beta-hydroxysteroid dehydrogenases type1and type7can both participate in synthetic estrogens from estrogen and degrade testosterone todihydrotestosterone. Recent research widely accepted that estrogen can promoteestrogen receptor positive breast cancer cells proliferation and androgen can have theopposite effect. So we think17beta-hydroxysteroid dehydrogenases type1and type7May become a target of treatment and diagnosis of breast cancer. This paper studies the effect of cell proliferation by the catalytic substrates whichare the above two kinds of enzymes and focused on cell cycle regulation when17beta-hydroxysteroid dehydrogenases type7changes in breast cancer cells. We foundthat above enzyme influence the S phase of cancer cells and there is positivecorrelation between the expression of17beta-hydroxysteroid dehydrogenases type7and cyclin E1.At present, we do more researches about17beta-hydroxysteroid dehydrogenasestype1than type7. Because17beta-hydroxysteroid dehydrogenases type1isconsidered as a key enzyme for the transformed from estrone into estradiol and ourmajor topic is aimed at the inhibitor of17beta-hydroxysteroid dehydrogenases type1.There are two key methods to quell the enzyme activity and both methods arepublished now. One is to reduce gene expression and the transcription of protein willsuppressed. The other one is to use inhibitor which is designed by the protein structureinhibit the activity of the enzyme. Small interfering ribonucleic acid can reduce geneof17beta-hydroxysteroid dehydrogenases type1expression and inhibit proliferationof two breast cells lines in vitro. The effect of small interfering ribonucleic acid isexactly and specificity, however, the small snippets or even modification ofribonucleic acid can little stable exist in the blood or tissue of human body. Then thesynthetic inhibitor become the important way. With the knowledge development ofthe structure of17beta-hydroxysteroid dehydrogenases type1, there are many kindsof inhibitors be found. One of these kinds including RB-225-50and EM–1745, theyshowed more significantly inhibit17beta-hydroxysteroid dehydrogenases type1inthe purified protein of than in the cells.Structurally, the inhibitor has both hydrophilic (adenine) and hydrophobic(steroid estrogen) parts is kind of amphiphilic polymer, so it hard to across cancer cellmembranes. In order to solve the above problem, we select liposome as the inhibitorcarrier to block the function of17beta-hydroxysteroid dehydrogenases type1.Liposome is an artificial lipid microparticulate with the structure of the lipidbilayer. It has the following advantages as the inhibitor carrier to prolong drugduration, combat multi-drug resistance reduce toxicity and sustained-release in some degree. Our study is expected to encapsuled the inhibitor in liposome and deliver theinhibitor into cancer cells. Furthermore, the inhibitor block the function of theenzymes. In our research we try to use poly (ethylene oxide)-poly (propyleneoxide)-poly (ethylene oxide)（F-68）modified liposome, positively charged liposomeimprove intake liposome by cell and the pre-liposome already on the market. At lastwe determine the lecithin, cholesterol, and octadecylamine as the main materials ofliposome. This liposome with suitable particle size will have a large uptake when itlabelled with fluorescein isothiocyanate. Finally we get a kind of stable liposome withsimple way to prepare.This study used the above liposome as a carrier of inhibitor of17β-HSD1deliver it into cells which is high level of17β-HSD1. And the rate of inhibitioncompared to the control was not significantly difference. The experiment confirmedthis kind of liposome was not suitable to be the carrier of the enzyme inhibitorsinsteroid metabolism. We may use micelle as a carrier develier the inhibitor of17β-HSD1. However，the experiment of nano drug carrier technology was used onthefunction of the family of17β-HSD for thefirst time, and it provides a newdirectionof research. |
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