Knockdown of cancerous inhibitor of protein phosphatase 2A may sensitize metastatic castration-resistant prostate cancer cells to cabazitaxel chemotherapy.

Cancerous inhibitor of protein phosphatase 2A (CIP2A) is a recently identified human oncoprotein that can stabilize some proteins by inhibiting degradation mediated by protein phosphatase 2A (PP2A), and its level in cancer is associated with resistance to chemotherapy. However, whether CIP2A could increase chemoresistance of prostate cancer (PCa) cells to chemotherapeutic agent cabazitaxel remains unclear. To determine whether CIP2A serves as a potential therapeutic target of human PCa, we utilized small interference RNA (siRNA) to knock down CIP2A expression in human PCa cells and analyzed their phenotypic changes. The data demonstrated that CIP2A was significantly elevated in mCRPC cell lines C4-2 and ARCaP(M) at both the mRNA and protein levels. CIP2A silencing led to decreased proliferation and enhanced chemosensitivity and apoptosis to cabazitaxel in human PCa cells, as well as reduced Akt phosphorylation. Our data suggesting critical roles of CIP2A in PCa cells chemoresistance to cabazitaxel and raising the possibility of CIP2A inhibition as a promising approach for chemosensitization of metastatic castration-resistant prostate cancer (mCRPC).

Nano Pd-Decorated Manganese Dioxide Nanosheets for Effective Photothermal Chemotherapy.

A drug delivery system based on the palladium and manganese dioxide composite (FP-Pd@MnO2) is designed and prepared for the first time. The FP-Pd@MnO2 allows doxorubicin (DOX) loading as high as 58% in weight. The rapid release of DOX from FP-Pd@MnO2 is regulated via pH reduction, ascending glutathione concentration, and near-infrared (NIR) stimulus, which is advantageous to control drug release in the tumor site. The photothermal effect of FP-Pd@MnO2 with wide and strong NIR optical absorbance is positively correlated with its concentration. As irradiated with an 808 nm laser, MDA-MB-231 cells and its tumor on mice with FP-Pd@MnO2/DOX administration are significantly suppressed, corroborating the preferable curative effect of combined photothermal therapy and chemotherapy with this agent.

[Preparation and evaluation of a new type of amino-bonded silica chromatographic stationary phase for the determination of lactose].

A method for the separation and determination of lactose and sucrose using high performance liquid chromatography-refractive index (HPLC-RI) detection base on the prepared amino-bonded silica gel chromatographic stationary phase was established. The method was accorded to the content determination method in Pharmacopoeia of the People's Republic of China (2015). Then, a series of chromatographic behaviors of lactose and sucrose such as the retention times, resolutions and peak area stabilities were investigated on three different types of amino-bonded silica columns (300 mm×4.6 mm, 5 µm). The mobile phase was acetonitrile-water (70:30, v/v) with isocratic elution, the flow rate was 1.0 mL/min and the injection volume was 10 µL. The resolution of lactose and sucrose was 3.03 by isopropyl side chain protected amino column, and the peak shape of each target compound was good. The relative standard deviation (RSD) of peak area of lactose was 1.14%, less than 2.0% prescribed in the Pharmacopoeia of the People's Republic of China (2015). Therefore, this method meets the requirements of lactose content determination, and is suitable as the quality control method in the above mentioned Pharmacopoeia.

Antitumor activity of nimotuzumab in combination with cisplatin in lung cancer cell line A549 in vitro.

Nimotuzumab, a humanized IgG1 monoclonal antibody against epidermal growth factor receptor (EGFR), increases radiosensitivity in lung cancer. Cisplatin is an effective antitumor agent in lung cancer. In the present study, the antitumor activity of nimotuzumab combined with cisplatin was investigated in A549 lung cancer cells. Viability, cell cycle distribution and cyclin D1 expression were assessed following treatment with nimotuzumab alone, cisplatin alone, nimotuzumab in combination with cisplatin, and nimotuzumab followed sequentially by cisplatin. The inhibitory effect on cell viability of nimotuzumab sequentially followed by cisplatin was higher compared with cisplatin alone (82.17±1.62 vs. 56.97±1.42%). Compared with treatment by cisplatin alone, cell cycle analysis by flow cytometry demonstrated that the percentage of cells in the G0/G1 phase was increased when A549 cells were treated with nimotuzumab followed sequentially by cisplatin (P<0.01). However, the proportion of cells in G0/G1 phase was decreased when A549 cells were treated with nimotuzumab and cisplatin simultaneously compared with cisplatin alone (P<0.05). Cyclin D1 expression was decreased in all chemotherapy treatment groups; the most significant decrease was in A549 cells treated with nimotuzumab followed sequentially by cisplatin. Nimotuzumab may enhance the antitumor activity of cisplatin on A549 cells. The cell cycle arrest at G0/G1 observed may have been due to decreased cyclin D1 levels. Potential antagonism was identified when A549 cells were treated with nimotuzumab and cisplatin simultaneously, indicating that targeted therapy may be more effective when administered prior to conventional chemotherapy.

[Determination of triterpenoic acid isomers in Eriobotryae folium using high performance liquid chromatography on C30 column].

A rapid and easy assay method for four triterpenoic acid isomers in Eriobotryae folium was established. The sample was extracted with methanol, then separated on a C30 column (250 mm x 4.6 mm, 5 microm) at 20 degrees C using acetonitrile-water (95 : 5, v/v) as the mobile phase at a flow rate of 1.0 mL/min. The target compounds were simultaneously detected at 210 nm, and the injection volume was 10 microL. The validation was carried out and the resolution (R > or = 2.2), the precision (RSD < or = 1.1%), the linearity (r > or = 0.999 2), the repeatability (RSD < or = 4.4%), and the recovery (range from 95.4% to 101.7%, RSD < or = 4.8%) were acceptable. The method is reliable for the quantification of the four triterpenoic acid isomers by HPLC on C30 column.

Determination of oleanolic acid and ursolic acid in Chinese medicinal plants using HPLC with PAH polymeric C18.

BACKGROUND: The RP-HPLC resolution of two triterpenic acid isomers was unstable. OBJECTIVE: To separate the oleanolic acid (OA) and ursolic acid (UA) simply within RP-HPLC. MATERIALS AND METHODS: The separation ability of five stationary phases was studied with the retention effect of their carbon loads. Also the resolution effects of mobile phase composition and different column temperatures were systematically investigated by using Drylab(®) (Rheodyne LLC.) after evaluating chromatograms automatically. RESULTS: The best available resolution of two bioactive isomers was achieved (r = 3.4) via using PAH (polycyclic aromatic hydrocarbons) polymeric C18 bonded phase column. The chromatographic system was applied to the quantification in ten Chinese medicinal plants and the validation was carried out and the precision (RSD ≤1.34%), the linearity (r ≥ 0.9998) and the recovery (range from 92.1% to 102.6%) were acceptable. CONCLUSION: It is clear that the method was simple, rapid and reliable for the quantification of two compounds in new HPLC method within PAH polymeric C18.