| Cervical cancer is the most prevalent malignancy of the femalereproductive system in China.In the global,466000new cases every year,80%cases have happened in developing countries, China will account for28.8%ofall new cases, to131500. In recent years, with in some parts of the humanpapilloma virus (HPV) infection rates rising and changes of social life[4], theincidence of cervical cancer in our country is highest of all genecologymalignancy tumors.And the incidence of cervical cancer among young womenare reportedly on the rise.Before the1980s, surgery and radiation therapy is the main treatment ofcervical cancer, cervical cancer belongs to the chemical drug treatment resistcancer[6]. Because the young patients with cervical cancer and Locally adancedcervical cancer (LACC)[8]is on the rise,radiation therapy caused irreversibledamage of the reproductive and ovarian,that discourages young cerical cancertreatment of progress. In1983, cervical cancer is proved to be chemotherapysensitivity tumor[9], and in the light of LACC puts forward the concept of newadjuvant chemotherapy (NACT): before surgery or radiation therapy combinedwith2～3course of chemotherapy. The NACT make tumor smaller and turnthe clinical stages reverse, the patients that can't do the operation as a viableextensive abdominal hysterectomy, eliminate the clinical transfer, reduce thepelvic lymph node and distant metastasis rate, avoid and reduce big doseradiation and tract irreversible damageto the ovary and the reproductive.Peoplewere gradually pay attention to the chemotherapy treatment of cervical cancer,especially in the recent10years, comprehensive treatment on cervical cancerhas caught more attention and become an important strategy of cervical cancer.But chemical drugs kill tumor cells, and at the same time, also cause serious side effects, that bring pain for patients. How to reduce or eliminate the sideeffects of chemotherapy, and improve the close tumor tissue specific for cancertreatment have became insurmountable obstacle.Tumor targeting treatment is a method that specific carrier delivery drugsor other active material reach specific tissues and play its role in thisarea,enhance the action of a medical treatment meanwhile reduce the sideeffects. Malignant tumor targeting treatment has become a hot and key researchin home and abroad. Targeting treatment consist of active targeting and passivetargeting. FA receptors belong to a ligand system of active targeted drugdelivery vehicle. In view of FA receptors are only over-expressed in tumor cells,it has good specificity of tumor cells, tumor specific therapeutic that use folicacid receptor have caught attention by people.Paclitaxel (PTX) has a good therapeutic effect for a variety of malignanttumors, and is used as a line broad-spectrum cancer drugs, however, due to thelack of resources, low lipid-soluble, the side effects and higher shortcomings,its clinical application is greatly limited. In order to play better curativeeffect,people try to change the drug formulations, so as to reduce its side effects,and increase drug concentration in target sites.According to the theory of tumor targeting treatment, this study choosesamphiphilic biodegradable polymer polyethylene glycol (peg) and with lateralof carboxyl of poly (lactic acid-carbonate) embedded segment copolymersMPEG-b-P (LA-co-MCC) with paclitaxel bonding, made of polymer precursordrug, and it carries folic acid ligand polymer MPEG-b-P (LA-co-DHP/FA)assembly into nanometer micelle. Increase in water solubility of taxol, prolongdrug in the body of the cycle time, improve the bioavailability, reduce the sideeffects, and may-the expression of folate receptors with active target of tumorcells, so as to improve the curative effect. To discuss the inhibition of the tumor,the mice U14cervical cancer cell lines for the internal and external efficacy experiment, and related inspection so as to provide theoretical basis for clinicalapplication.Purpose:To use mice U14cervical cancer cells for the internal and externalefficacy experiment, to discuss the inhibition of the tumor.Methods:In internal experiment, detect the inhibition of different drugs on the tumorcells by the MTT method, detect cell apoptosis by the Annexin V-PI doubledyed method; In external experiment,establish U14mice cervical cancer model,use FA-PTX micelle, PTX micelle, PTX to treat the mice model, calculationtumor inhibition rate; detect the cell apoptosis rate by flow cytometric andTUNEL method; observed tumor tissue and its organizition form by HE; detectCaspase-3and Bcl-2protein expression by immunohistochemical method;observe mice survival condition and survival time.Results:1. Nano micelle carrier with good dispersion is sphere and particle sizedistribution is uniformity, diameter and dispersion coefficient is80nm and0.2.PTX is protected in the hydrophobic core and the content of PTX is22.5%.Because 'shell' was consist of hydrophilic PEG segment, it can stabilizemicelles and has strong solubilizing ability to drug. Moreover,'shell' canprotect micelles from immune system attacks. critical micelle concentrationsmall, income in the micelle for nanoparticles in medicine rate is higher andstable.2.In external experiment⑴The inhibition of different drugs on the tumor cells by the MTT method,the inhibition rate of PTX, PTX micelle, FA PTX micelle U14cervical cancercells is concentration and time-dependent. ⑵Detect cell apoptosis by Annexin V-PI double dyed method, conjugatedpolymer micelles and taxol can induced cell apoptosis and to achieve tumorinhibition, the cell apoptosis rate is in order: FA PTX micelle> PTX micelle>PTX.⑶Different drugs impact on U14cervical cancer cells, we can directlyobserved from the morphology, conjugated polymer paclitaxel micelles haveapparent inhibition, and the cell inhibition can equate pure taxol, pure taxol ismore obvious poisoned.3.In internal experiment:⑴In three drugs, The inhibition of FA PTX micelle is best, the inhibitionrate is in order: FA PTX micelle> PTX micelle> PTX.⑵Detect the cell apoptosis by flow cytometric and TUNEL method, threekinds of medicines can induce tumor cell apoptosis and to achieve tumorinhibition, the three apoptosis rate is in order: FA PTX micelle> PTXmicelle> PTX.⑶Observed by pathology, through the FA-mediated active targetingtreatment, medicine nanoparticles can reach tumor tissue to achieve tumorinhibition and cause inflammation response.⑷Detected Caspase-3, Bcl-2expression by immunohistochemical method,its drug apoptosis mechanisms is relevant with regulation of level oftumor-suppressor genes and cancer genes.⑸Survival experiments show that, conjugated polymer paclitaxel micellescan reduce drug side effects, prolong the survival time.Conclusion:1. Nano micelle carrier is made successfully, PTX was protected in thehydrophobic core, it can stabilize micelles and has strong solubilizing ability todrug. Moreover,'shell' can protect micelles from immune system attacks.2. The inhibition on U14cervical cancer cells of Taxol, PTX micelle,FA PTX micelle is concentration and time-dependent, nano micelle carrier did not change paclitaxel antitumor function, and taxol cytotoxic effects is the mostobvious.3. The effect of FA PTX micelle is better than taxol. The treatment effecton mice U14cervical cancer is most obvious, FA PTX micelle can reducedrug side effects, prolong the survival time,,shows the characters of targeteddrugs bioavailability, extended-release and active targeted advantage.4. Conjugated polymer paclitaxel micelles induce cell apoptosis to achievetumor inhibition;its drug apoptosis mechanisms is relevant with regulation oflevel of tumor-suppressor genes and cancer genes.
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