Résumé
Overexpression of cytokine-induced apoptosis inhibitor 1 (CIAPIN1) contributes to multidrug resistance (MDR) in breast cancer. This study aimed to evaluate the potential of CIAPIN1 gene silencing by RNA interference (RNAi) as a treatment for drug-resistant breast cancer and to investigate the effect of CIAPIN1 on the drug resistance of breast cancer in vivo. We used lentivirus-vector-based RNAi to knock down CIAPIN1 in nude mice bearing MDR breast cancer tumors and found that lentivirus-vector-mediated silencing of CIAPIN1 could efficiently and significantly inhibit tumor growth when combined with chemotherapy in vivo. Furthermore, Western blot analysis showed that both CIAPIN1 and P-glycoprotein expression were efficiently downregulated, and P53 was upregulated, after RNAi. Therefore, we concluded that lentivirus-vector-mediated RNAi targeting of CIAPIN1 is a potential approach to reverse MDR of breast cancer. In addition, CIAPIN1 may participate in MDR of breast cancer by regulating P-glycoprotein and P53 expression.
Sujets)
Animaux , Femelle , Humains , Antibiotiques antinéoplasiques/usage thérapeutique , Tumeurs du sein/traitement médicamenteux , Doxorubicine/usage thérapeutique , Résistance aux médicaments antinéoplasiques/génétique , Extinction de l'expression des gènes , Protéines et peptides de signalisation intracellulaire/génétique , Technique de Western , Tumeurs du sein/génétique , Carcinomes/traitement médicamenteux , Carcinomes/génétique , Modèles animaux de maladie humaine , Gènes MDR , Vecteurs génétiques/génétique , Inhibiteurs de croissance/génétique , Protéines et peptides de signalisation intracellulaire/métabolisme , Lentivirus/génétique , Souris de lignée BALB C , Souris nude , Glycoprotéine P/effets des médicaments et des substances chimiques , Interférence par ARN , Petit ARN interférent/génétique , /effets des médicaments et des substances chimiquesRésumé
As ragweed becomes widespread over China, ragweed pollenosis tends to be more frequent. Incidence of ragweed pollenosis is about 1.04% in Qingdao district. To elucidate ragweed as an allergen in the development of bronchial asthma, ragweed pollen extract inhalation airway provocation tests (APT) were studied in 55 patients with ragweed pollenosis. A single dosage of 9,000 PNU ragweed pollen extract was applied and positive response was defined as more than 35% fall in SGrs at the dose of PT35-Grs. Among 55 patients, positive APTs were found in 27 cases (49%), dual late-phase responses in 11 patients, single late-phase responses in 2 patients in the complicated asthma group. Late-phase responses were related to the increased specific IgE and strong positive skin test response (wheal > 11 mm). The results suggested ragweed pollen was one of the important allergens causing bronchial asthma. There was airway hyperresponsiveness to ragweed pollen in some patients (20%) with ragweed pollenosis without asthmatic symptoms.