Correlation of OCTN2 with the chemosensitivity of prostate cancer cells to oxaliplatin / 中国药房

OBJECTIVE To study the correlation of novel organic cation transporter 2 （OCTN2） with the chemosensitivity of prostate cancer cells to oxaliplatin. METHODS Tumor samples of patients receiving radical prostatectomy were collected， and OCTN2 protein was detected with immunohistochemistry； the primary cells of the specimen were cultivated to obtain prostate cancer cell line. Inductively coupled plasma mass spectrometry was used to detect the uptake of low concentration （0.1 μmol/L） of oxaliplatin by cancer cells. Real-time PCR and Western blot were used to detect the mRNA and protein expressions of OCTN2 in cancer cells； the prostate cancer cells with the highest and lowest expression of OCTN2 protein were selected， and IC50 of oxaliplatin to prostate cancer cells was analyzed by ATP-TCA method. The inhibitory rate of plasma peak concentration of oxaliplatin （50 μmol/L） to prostate cancer cells was detected by MTT assay. Spearman method was used to analyze the relationship of the uptake of oxaliplatin by prostate cancer cells with inhibitory rate of oxaliplatin to prostate cancer cells and 505916443@qq.com mRNA expressions of OCTN2. RESULTS OCTN2 was located on the membrane of cancer cells， and the uptake of zjdtztougao@163.com oxaliplatin by cancer cells was 0.283±0.264 （n＝12）mRNA and protein expression of OCTN2 varied significantly among different cancer cells. The sensitivity of cancer cells with high expression of OCTN2 to oxaliplatin （IC50 of 4.61 μmol/L） was higher than that of cancer cells with lower expression of OCTN2 （IC50 of 26.23 μmol/L）. The inhibitory rate of oxaliplatin to cancer cells was （25.4±10.8）% （n＝12）. There was a correlation between the uptake of oxaliplatin by prostate cancer cells and the inhibition rate of oxaliplatin to prostate cancer cells and mRNA expression of OCTN2 （P＜0.05）. CONCLUSIONS High-expressed OCTN2 may promote the uptake of oxaliplatin by prostate cancer cells， and its expression can serve as a reference for predicting the sensitivity of prostate cancer cells to oxaliplatin chemotherapy.

Effects of icarⅡn on viability, migration and invasion of prostate cancer cells / 中国病理生理杂志

AIM:To investigate the effects of icarⅡn on the viability, migration and invasion of the prostate cancer lines Du145 and PC3.METHODS:Du145 cells and PC3 cells were treated with icarⅡn at different concentrations (0, 5, 10, 20, 40 or 80 μmol/L), and the cell viability was measured by CCK-8 assay.The cell migration and invasion abilities were detected by Transwell assay.The protein expression of Notch-1, matrix metalloproteinase (MMP)-2, MMP-9 and hairy/enhancer of split-1 (Hes-1) was determined by Western blot.RESULTS:The results of MTT assay revealed that icarⅡn inhibited the viabilitiy of Du145 cells and PC3 cells in a dose-dependent manner.The maximal effect was at dose of 40 μmol/L.IcarⅡn treatment significantly decreased the abilities of migration and invasion of Du145 cells and PC-3 cells.Moreover, the protein expression of Notch-1, MMP-2, MMP-9 and Hes-1 was dramatically reduced after icarⅡn treatment.CONCLUSION:IcarⅡn inhibits prostate cancer cell viability, migration and invasion by decreasing the protein expression of Notch-1, MMP-2, MMP-9 and Hes-1.

Androgen-like effects of Cordyceps sinensis and its impact on the radiosensitivity of VCaP prostate cancer cells / 中华放射肿瘤学杂志

Objective To investigate the androgen-like effects of Cordyceps sinensis (CS) and its impact on the radiosensitivity of VCaP prostate cancer cells.Methods The hormone levels and weight index of reproductive organs in mice were determined after gavage with CS.Clonogenic assay was performed to determine the impact of CS on the radiosensitivity of VCaP cells.The 3-(4,5-dimethylthiazol-2-yl)-5 (3-carboxymethonyphenol)-2-(4-sulfophenyl)-2H-tetrazolium assay,flow cytometry,and tumor xenografts in nude mice were performed to determine the effects of CS on the proliferation of VCaP cells (androgen receptor-positive) and PC-3 cells (androgen receptor-negative) in vitro and in vivo.Serum prostate-specific antigen (PSA) levels in nude mice were evaluated.Data were analyzed by one-way analysis of variance or ttest.Results The testosterone level and weight of prostate in mice were significantly higher in the CS group than in the control group ((8.28± 1.94) vs.(2.08± 1.24) ng/ml,P=0.023;(0.53±0.04) vs.(0.31 ± 0.04) mg/g,P =0.006).The radiosensitivity enhancement ratio (ratio of D0 values) was 0.80.The viability of VCaP cells was significantly higher in the CS group than in the control group (1.32 ± 0.07 vs.0.66 ±0.02,P=0.000),and colony forming efficiency was significantly enhanced in the CS group than in the control group (57.0％ ± 1.9％ vs.47.0％ ± 0.6％,P =0.005).VCaP tumor xenografts in nude mice were inclined to grow faster in the CS group than in the control group,and the serum PSA level in the CS group was significantly higher than that in the control group ((0.66 ± 0.04) vs.(0.26 ±0.06) ng/ml,P =0.000).However,CS had no effect on PC-3 cells at the working concentration.Conclusions CS has the androgen-like effects.It may also promote the proliferation and reduce the radiosensitivity of androgen receptor-positive VCaP cells.

Influence of Estrogen and Polyamines on Mifepristone-induced Apoptosis in Prostate Cancer Cells / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Although androgens are the main steroids controlling the growth of prostate glands, estrogens are also important in the regulation of its growth. Prostate cancer cells, like other cancer cells, maintain high levels of polyamines. In LNCaP cells, apoptosis is induced by mifepristone. During the process of cell death, the regulation of ROS production, caspase-3 activation and poly (ADP-ribose) polymerase cleavage were investigated in the presence of estrogen and polyamines to identify their possible roles. MATERIALS AND METHODS: The cell growth was assessed using the MTT assay, and the intracellular ROS production by the DCFH-DA assay. The p53 protein expression, activation of caspase-3 and PARP cleavage were checked by Western blotting, with specific antibodies to each. RESULTS: The growth and viability of the cells were significantly inhibited, in a dose- and time-dependent manners, by mifepristone (MIF) treatment. The production of ROS were dependent on the MIF dosage. The activation of caspase-3 and cleavage of PARP also increased with the duration of MIF treatment. The expression of p53 protein also increased with increases in the MIF incubation time. E2 severely inhibited the ROS production, caspase-3 activation and PARP cleavage. However, polyamines only inhibited the ROS production, without influencing the caspase-3 activation or PARP cleavage. CONCLUSION: In LNCaP cells, MIF induces apoptosis through ROS production. The expression of p53 protein, caspase-3 activation and PARP cleavage accompanied the process of apoptosis. The apoptotic processes were inhibited by E2, but polyamines only inhibited the ROS production, implying the multifunctional role of E2, in addition to its role as a free radical scavenger.

Effect of Synthetic Tyrosine Kinase Inhibitor(ZM260603) on the Growth of Prostate Cancer Cell Lines: Differences According to Androgen Dependency and Bcl-2 Expression / 대한비뇨기과학회지

PURPOSE: We determined the effect of tyrosine kinase inhibitor(TKI), ZM260603 on the growth of prostate cancer cell lines. MATERIALS AND METHODS: Using the synthetic TKI, ZM260603, cytotoxicity test and cell cycle analysis were performed on LNCaP, DU-145 and PC3 prostate cancer cell lines. The bcl-2 and bax protein expressions were observed in PC3 prostate cancer cell line by western blotting. The inhibitory effect of TKI was determined under the presence or absence of dehydrotestosterone, in androgen-dependent LNCaP prostate cancer cell line. RESULTS: The synthetic TKI, ZM260603 showed definite cytotoxicity on all prostate cancer cell lines studied regardless of androgen-dependency. The IC50 were 0.35+/-0.08microM, 0.12+/-0.06microM and 0.21+/-0.09microM for LnCaP, DU-145 and PC-3 cell lines, respectively. The G0/G1 phase arrests were observed commonly in all of these cell lines by flowcytometric analysis. Decrement in bcl-2 expression and increment of bax protein expression in the PC-3 cell line was observed by western blotting. The IC50 of hormone-dependent LNCaP prostate cancer cell line on TKI was increased about four folds by the addition of dihydrotestosterone. CONCLUSIONS: Our results suggest that the changes in the expression of bcl-2 and bax proteins are related with inhibitory process of the synthetic TKI, ZM260,603 on the growth of prostate cancer cell lines. Androgen seems to act as compromising or weakening the effects of TKI in androgen-dependent prostate cancer cell line, although the exact relationships between androgen-dependency and bcl-2 expression are unclear.

ISOFLAVONES INDUCED APOPTOSIS IN PROSTATE CANCER CELL PC-3 / 营养学报

Objective: To explore the mechanisms of the effect of isoflavone in reducing prostate cancer incidence throught studying the effects of isoflavone on apoptosis in PC-3 cell. Methods: Prostate cancer cell PC-3 was grown in RPMI 1640 medium supplemented with 10% bovine serum and 10 000 U/ml of penicillin/streptomycin in an incubator maintained at 5% CO 2 95% air and 100% humidity at 37 ℃. The respective test compound was added in fresh medium and the control cell received only the vehicle (MDSO). Apoptosis of PC-3 cells was analyzed by cell morphology under light microscope, agarose gel electrophoresis and flow cytometry. Results: Exposure of PC-3 cell to 50 ?mol/L GS, 75 ?mol/L DA and 75 ?mol/L GL after 72 h, the cell morphology indicated typical features commonly used to define apoptosis; agarose gel electrophoresis demonstrated laddered electrophoretic profiles of oligonucleosomal DNA fragments indicative of apoptosis, and flow cytometric analysis revealed a hyperdiploid population in the tested cells. Conclusion: Isoflavones could induce apoptosis in prostate cancer cells PC-3 and it may be the main cause of their role in cancer inhibition.