Inhibiting the m6A Reader IGF2BP3 Suppresses Ovarian Cancer Cell Growth via Regulating PLAGL2 mRNA Stabilization.

Background: The oncogene IGF2 mRNA binding protein 3 (IGF2BP3) could function as an m6A reader in stabilizing many tumor-associated genes' mRNAs. However, the relevant oncogenic mechanism by which IGF2BP3 promotes ovarian cancer growth is largely unknown. Methods: The IGF2BP3 expression in ovarian cancer was identified by retrieving the datasets from The Cancer Genome Atlas (TCGA). GEO datasets evaluated the relevant signaling pathways in IGF2BP3 knockdown in ovarian cancer cells. IGF2BP3 positive correlation gene in TCGA was calculated. MTS proliferation assay was identified in IGF2BP3 knockdown and rescued by PLAG1 like zinc finger 2 (PLAGL2) overexpression in ES-2 and SKOV3 cells. Bioinformatic analysis and RIP-qPCR were predicted and identified the IGF2BP3 binding site and PLAGL2 mRNA stability. The animal experiment identified IGF2BP3 proliferation inhibition. Results: IGF2BP3 was upregulated in ovarian cancer tissue and cells. The depletion of IGF2BP3 in ovarian cancer cells leads to an enhancement of the pathway involved in cellular proliferation and mRNA stability. IGF2BP3 positive correlation suppressed pro-proliferation gene PLAGL2. IGF2BP3 knockdown suppressed ovarian cancer cell proliferation and was rescued by PLAGL2 overexpression. Luciferase reporter assay confirmed that IGF2BP3 could bind to 3'-UTR of PLAGL2 to maintain the mRNA stability. Further, in in vivo experiments, IGF2BP3 knockdown suppressed ovarian cancer cell proliferation via inhibiting PLAGL2 expression. Conclusion: All of these indicate that PLAGL2 mediates the main function of IGF2BP3 knockdown on ovarian cancer proliferation inhibition through mRNA stability regulation.

Carbon Nitride-Based siRNA Vectors with Self-Produced O2 Effects for Targeting Combination Therapy of Liver Fibrosis via HIF-1α-Mediated TGF-ß1/Smad Pathway.

Hypoxia is an important feature, which can upregulate the hypoxia-inducible factor-1α (HIF-1α) expression and promote the activation of hepatic stellate cells (HSCs), leading to liver fibrosis. Currently, effective treatment for liver fibrosis is extremely lacking. Herein, a safe and effective method is established to downregulate the expression of HIF-1α in HSCs via targeted delivery of VA-PEG-modified CNs-based nanosheets-encapsulated (VA-PEG-CN@GQDs) HIF-1α small interfering RNA (HIF-1α-siRNA). Due to the presence of lipase in the liver, the reversible release of siRNA can be promoted to complete the transfection process. Simultaneously, VA-PEG-CN@GQD nanosheets enable trigger the water splitting process to produce O2 under near-infrared (NIR) irradiation, thereby improving the hypoxic environment of the liver fibrosis site and maximizing the downregulation of HIF-1α expression to improve the therapeutic effect, as demonstrated in liver fibrosis mice. Such combination therapy can inhibit the activation of HSCs via HIF-1α-mediated TGF-ß1/Smad pathway, achieving outstanding therapeutic effects in liver fibrosis mice. In conclusion, this study proposes a novel strategy for the treatment of liver fibrosis by regulating the hypoxic environment and the expression of HIF-1α at lesion site.

Detection of trace mercury ions in water with a bovine-serum-albumin-modified Au@SiNWA surface-enhanced-Raman-scattering sensor.

Accurate detection of mercury ions (Hg2+) in water is of great importance for environmental protection. Here, a surface-enhanced Raman scattering (SERS) sensor using bovine-serum-albumin-modified gold-silicon nanowire arrays (Au@SiNWAs) is used to detect the ions. The SiNWAs were grown via chemical etching; the addition of modified gold particles on the surface formed Au@SiNWAs to increase the surface activity. The Raman enhancement factor was as large as ∼2.52 × 105, which was also confirmed with finite-difference time-domain simulations. The detection limit for Hg2+ ions in water was as low as ∼10-12 M, which is much lower than that stipulated by the United States Environmental Protection Agency's maximum residue requirements for drinking water. Furthermore, the SERS intensity was linear with the log of the Hg2+ concentration between 1 pM and 100 nM, with a correlation coefficient of 0.992. There was no significant interference when other metal ions were present, which shows the excellent selectivity of the SERS sensor. Unknown Hg2+ concentrations in water can be readily determined in an accurate and reliable manner, with a relative standard deviation of ∼9.21%.

Facile synthesis of Au nanoparticle-coated Fe3O4 magnetic composite nanospheres and their application in SERS detection of malachite green.

A facile method for synthesizing Au nanoparticle-coated Fe3O4 magnetic composite nanospheres (Fe3O4@Au MCS) via seed-mediated growth and iterative reduction is reported. The nanospheres were then successfully used to detect malachite green (MG) residues in water bodies via surface-enhanced Raman scattering (SERS) technique. Fe3O4@Au MCS has excellent optical properties and superparamagnetism; it can be dispersed into the solution to fully adsorb target molecules and then collected with a magnet to increase the molecular density and the number of SERS hot spots. Magnetic enrichment was superior to conventional detection method. The limit of detection for MG was 10-7 M and the enhancement factor was 1.1 × 105. The logarithm of the SERS intensity of the characteristic peak at 1618 cm-1 exhibited a linear relationship with the logarithm of the MG concentration over the range of 10-3- 10-7 M, with a correlation coefficient of 0.966. The Fe3O4@Au MCS had good uniformity of SERS signals, with a 18.59% relative standard deviation for the SERS intensity. MG detection in aquaculture water conformed with the established quantitative regulations. The SERS spectrum calculated with density function theory for MG adsorbed on Fe3O4@Au MCS was very close to the experimental spectrum, which verified enhancement by the substrate. Overall, Fe3O4@Au MCS enabled ultrasensitive, quantitative SERS detection of MG.

Rapid determination of 1,3-propanediol in fermentation process based on a novel surface-enhanced Raman scattering biosensor.

The production of 1,3-propanediol (1,3-PDO) is an important fermentation process. However, 1,3-PDO could not be distinguished separately and efficiently in fermentations previously because it has a highly similar molecular structure to the feedstock glycerol (GLY) and by-product lactic acid (Lac), which leads to the difficulty of quantification. In this paper, a low-cost and environmentally friendly biosensor based on surface-enhanced Raman scattering (SERS) technique was developed. Using it, the concentration of 1,3-PDO and Lac in a fermentation solution can be determined directly from their respective characteristic peaks in Raman spectroscopy. Moreover, by analyzing the respective contributions of 1,3-PDO, Lac, and GLY to the integrated intensities of the 2920 cm-1 Raman peak common to these three substances, the concentration of GLY could also be quantified. SERS study on various 1,3-PDO:GLY and Lac:GLY molar ratios were conducted to establish the proportional relationships of these compounds by analyzing the relationship between the concentration and the Raman peak intensities. The 1,3-PDO:Lac:GLY with serial concentration gradient was carried out to verify the relationship between the concentration and the Raman peak intensities by the high-performance liquid chromatography (HPLC) with relative deviations <25%. Concentrations of 1,3-PDO and Lac as low as 1 g/L and concentration of GLY as low as 4 g/L were analyzed to determine the limit of detection. Therefore, this new method allows the rapid quantification of 1,3-PDO, Lac and GLY concentrations on a SERS-based biosensor.

A rapid method to authenticate vegetable oils through surface-enhanced Raman scattering.

Vegetable oils are essential in our daily diet. Among various vegetable oils, the major difference lies in the composition of fatty acids, including unsaturated fatty acids (USFA) and saturated fatty acids (SFA). USFA include oleic acid (OA), linoleic acid (LA), and α-linolenic acid (ALA), while SFA are mainly palmitic acid (PA). In this study, the most typical and abundant USFA present with PA in vegetable oils were quantified. More importantly, certain proportional relationships between the integrated intensities of peaks centered at 1656 cm(-1) (S1656) in the surface-enhanced Raman scattering spectra of different USFA were confirmed. Therefore, the LA or ALA content could be converted into an equivalent virtual OA content enabling the characterization of the USFA content in vegetable oils using the equivalent total OA content. In combination with the S1656 of pure OA and using peanut, sesame, and soybean oils as examples, the ranges of S1656 corresponding to the National Standards of China were established to allow the rapid authentication of vegetable oils. Gas chromatograph-mass spectrometer analyses verified the accuracy of the method, with relative errors of less than 5%. Moreover, this method can be extended to other detection fields, such as diseases.

Ag@Au core-shell dendrites: a stable, reusable and sensitive surface enhanced Raman scattering substrate.

Surface enhanced Raman scattering (SERS) substrate based on fabricated Ag@Au core-shell dendrite was achieved. Ag dendrites were grown on Si wafer by the hydrothermal corrosion method and Au nanofilm on the surface of Ag dendritic nanostructure was then fabricated by chemical reduction. With the help of sodium borohydride in water, Au surface absorbates such as thiophene, adenine, rhodamine, small anions (Br(-) and I(-)), and a polymer (PVP, poly(N-vinylpyrrolidone)) can be completely and rapidly removed. After four repeatable experiments, the substrate SERS function did not decrease at all, indicating that the Ag@Au dendrite should be of great significance to SERS application because it can save much resource. Six-month-duration stability tests showed that the Ag@Au core-shell dendrite substrate is much more stable than the Ag dendrite substrates. We have also experimented on fast detection of Cd(2+) at 10(-8) M concentration by decorating single-stranded DNA containing adenine and guanine bases on the surface of this Ag@Au dendrite. Finite-difference time-domain simulations were carried out to investigate the influence of Au nanolayer on Ag dendrites, which showed that the local electric fields and enhancement factor are hardly affected when a 4 nm Au nanolayer is coated on Ag dendrite surface.

Approach for determination of ATP:ADP molar ratio in mixed solution by surface-enhanced Raman scattering.

The ATP:ADP molar ratio is an important physiological factor. However, in previous literatures, ATP and ADP could not be distinguished by Raman spectroscopy due to the high similarity of molecular structure. To challenge this problem, also considering that the γ phosphate group may interact with adenine group and cause a different variation of the Raman spectrum than that of ADP, a highly sensitive, low-cost, environment protecting, flexible and super-hydrophobic Au nanoparticles/cicada wing (Au/CW) substrate with three-dimension structure was fabricated and employed as an active surface-enhanced Raman scattering (SERS) substrate to detect the ATP:ADP molar ratios. The concentration as low as 10(-8)M for ATP and ADP was analyzed to determine the limit of detection. This SERS study on various ATP:ADP molar ratios demonstrates that ATP:ADP could be distinguished and the quantitative determination of ATP content was achieved. Moreover, a principle was speculated based on the molecular structures of ATP and ADP of the Raman peaks centered at ~685 and ~731cm(-1) to explain the linear relationship between the area ratio and the molar ratio. A new method has been developed for quantitative determination of ATP:ADP molar ratio based on Au/CW substrate by the SERS method.

Recyclable three-dimensional Ag nanoparticle-decorated TiO2 nanorod arrays for surface-enhanced Raman scattering.

Multifunctional Ag nanoparticle-decorated TiO2 nanorod arrays were prepared by two simple processes. TiO2 nanorod arrays were first fabricated by the hydrothermal route and then Ag nanoparticles were decorated on the nanorods by the chemical reduction impregnation method. Three-dimensional Ag/TiO2 arrays were used as an active substrate for surface-enhanced Raman scattering (SERS). The results show that the detection limit for rhodamine 6G (R6G) was as low as 10(-7)M and the Raman enhancement factor was as large as 10(5). After calibrating the Raman peak intensities of R6G, it could be quantitatively detected. More importantly, the photocatalytic activity of TiO2 provides a self-cleaning capability to the SERS substrate, which can be recycled and used to degrade many Ag surface adsorbates such as R6G, methyl orange, Congo red, and methylene blue after exposure to visible light. The absorbed small molecules can all be rapidly and completely removed from the SERS substrate, which has been successfully reused four times without a decrease in accuracy or sensitivity. Our results reveal that the unique recyclable property not only paves a new way to solve the single-use problem of traditional SERS substrates but also provides more SERS platforms for multiple detections of other organic molecular species.

Sexual dimorphism in epigenomic responses of stem cells to extreme fetal growth.

Extreme fetal growth is associated with increased susceptibility to a range of adult diseases through an unknown mechanism of cellular memory. We tested whether heritable epigenetic processes in long-lived CD34(+) haematopoietic stem/progenitor cells showed evidence for re-programming associated with the extremes of fetal growth. Here we show that both fetal growth restriction and over-growth are associated with global shifts towards DNA hypermethylation, targeting cis-regulatory elements in proximity to genes involved in glucose homeostasis and stem cell function. We find a sexually dimorphic response; intrauterine growth restriction is associated with substantially greater epigenetic dysregulation in males, whereas large for gestational age growth predominantly affects females. The findings are consistent with extreme fetal growth interacting with variable fetal susceptibility to influence cellular ageing and metabolic characteristics through epigenetic mechanisms, potentially generating biomarkers that could identify infants at higher risk for chronic disease later in life.

The meta-epigenomic structure of purified human stem cell populations is defined at cis-regulatory sequences.

The mechanism and significance of epigenetic variability in the same cell type between healthy individuals are not clear. Here we purify human CD34+ haematopoietic stem and progenitor cells (HSPCs) from different individuals and find that there is increased variability of DNA methylation at loci with properties of promoters and enhancers. The variability is especially enriched at candidate enhancers near genes transitioning between silent and expressed states, and encoding proteins with leukocyte differentiation properties. Our findings of increased variability at loci with intermediate DNA methylation values, at candidate 'poised' enhancers and at genes involved in HSPC lineage commitment suggest that CD34+ cell subtype heterogeneity between individuals is a major mechanism for the variability observed. Epigenomic studies performed on cell populations, even when purified, are testing collections of epigenomes, or meta-epigenomes. Our findings show that meta-epigenomic approaches to data analysis can provide insights into cell subpopulation structure.

Ag@SiO2 core-shell nanoparticles on silicon nanowire arrays as ultrasensitive and ultrastable substrates for surface-enhanced Raman scattering.

Ag nanoparticles (NPs) coated with silica nanolayers were decorated onto a large-scale and uniform silicon nanowire array (SiNWA) by simple chemical etching and metal reduction processes. The three-dimensional Ag/SiNWAs thus formed are employed as a substrate for surface-enhanced Raman scattering (SERS), and a detection limit for rhodamine 6G as low as 10(-16) M and a Raman enhancement factor as large as 10(14) were obtained. Simulation results show that two kinds of inter-Ag-NP nanogaps in three-dimensional geometry create a huge number of SERS 'hot spots' where electromagnetic fields are substantially amplified, contributing to the higher SERS sensitivity and lower detection limit. The excellent SERS stability of Ag/SiNWAs is attributed to the presence of the SiO2 nanolayer around Ag NPs that prevented the Ag NP surface from being oxidized. The calibration of the Raman peak intensities of rhodamine 6G and thiram allowed their quantitative detection. Our finding is a significant advance in developing SERS substrates for the fast and quantitative detection of trace organic molecules.

[Design, synthesis and evaluation of bis-nicotine derivatives as inhibitors of cholinesterases and beta-amyloid aggregation].

A novel series of bis-nicotine derivatives (3a-3i) were designed, synthesized and evaluated as bivalent anti-Alzheimer's disease agents. The pharmacological results indicated that compounds 3e-3i inhibited both acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) in the micromolar range (IC50, 2.28-117.86 micromol x L(-1) for AChE and 1.67-125 micromol x L(-1) for BChE), which was at the same potency as rivastigmine. A Lineweaver-Burk plot and molecular modeling study showed that these derivatives targeted both the catalytic active site (CAS) and the peripheral anionic site (PAS) of AChE. Besides, these compounds could significantly inhibit the self-induced Abeta aggregation with inhibition activity (11.85%-62.14%) at the concentration of 20 micromol x L(-1).

[Design, synthesis and evaluation of tacrine-methoxybenzene hybrids as cholinesterases inhibitors].

A series of tacrine-methoxybenzene hybrids (5a-5i) were designed, synthesized and evaluated as inhibitors of cholinesterases (ChEs). All the compounds had better ChEs inhibitory activities than tacrine with IC50 values at the nanomolar range. Compound 5h exhibited the strongest inhibition on acetylcholinesterase (AChE) with an IC50 value of 6.74 nmol x L(-1) and compound 5f showed the most potent inhibition on butyrylcholinesterase with IC50 value of 3.83 nmol x L(-1). Kinetic and molecular modeling studies showed that these hybrids targeted both the catalytic active site and the peripheral anionic site of AChE.

[Expression and clinical significance of IL-17 and IL-21 in patients with acute leukemia].

This study was aimed to investigate the effects of peripheral blood Th17 cells, IL-17 and IL-21 in the occurrence and development of acute leukemia. 60 patients with acute leukemia (19 patients with ALL, 41 patients with AML) were divided into non-remission group (group A, n=24), remission group (group B, n=36); 25 healthy volunteers were used as control group (group C). In addition to this, these 60 patients were divided into infection group (n=32) and non-infection group (n=28) on the basis of infection status. The concentration of IL-17 and IL-21 in the peripheral blood mononuclear cell culture supernatant after stimulation with anti-CD3 and anti-CD28 mAb were determined with ELISA. The expression of CD4+ IL-17+ cells was determined by flow cytometry. The results showed that (1) the concentrations of IL-17 and IL-21, and proportion of Th17 cells in group A and group B were much lower than those in group C (p<0.05); (2) the expression levels of IL-17 and IL-21, and the proportion of Th17 cells in group A were lower than those in group B (p<0.05); (3) the expression levels of Th17 and IL-17 in infection group were lower than those in non-infection group (p<0.05). It is concluded that Th17 cells may play important roles in the occurrence and development of acute leukemia through secreting IL-17 and IL-21, and their functional level can partially reflect the status of leukemia and can be used to evaluate the risks of infection in patients with leukemia.

[Perpetual impact of pregnancy-induced hypertension on blood pressure].

OBJECTIVE: To explore the perpetual impact of pregnancy-induced hypertension on blood pressure. METHODS: This retrospective cohort study included 782 cases of pregnant women who hospitalized at Kailuan Linxi hospital between October 1976 and August 2001. Patients were divided to with pregnancy induced hypertension (PIH, n = 77) group and non pregnancy induced hypertension (NPIH, n = 705) group. Patients were followed for 5 to 34 years (mean 18.8 +/- 5.3 years), the incidence of essential hypertension was obtained in July 2006-September 2007. RESULTS: (1) The cumulative incidence of essential hypertension during follow up was significantly high in PIH group (29.87%) than that in NPIH group 18.87% (P = 0.022). (2) At the final follow up, waist circumference; [(86.06 +/- 10.15) cm vs. (83.07 +/- 8.19) cm, P = 0.015], BMI [(24.83 +/- 4.01) kg/m(2) vs. (23.50 +/- 3.39) kg/m(2), P = 0.006], TC [(5.11 +/- 0.88) mmol/L vs. (4.89 +/- 0.94) mmol/L, P = 0.045] and GLU [(5.57 +/- 1.78) mmol/L vs. (5.20 +/- 1.38) mmol/L, P = 0.010] were all significantly higher in PIH group than those in NPIH group. (3) After adjustment of age and BMI, PIH was still significantly correlated with long-term systolic blood pressure levels (P = 0.048), fasting glucose level was also significantly associated with long-term systolic blood pressure. Age, BMI, white blood cell count and uric acid were also predictors for perpetual systolic and diastolic blood pressure levels. CONCLUSIONS: Incidence of essential hypertension in women with PIH was higher than that in women without PIH. After adjustment of covariates including age, BMI, and glucose, PIH was significantly associated with the level of systolic blood pressure. BMI, fasting glucose and cholesterol levels might contribute to the increase of systolic blood pressure in patients with PIH.

Proteome differences associated with fat accumulation in bovine subcutaneous adipose tissues.

BACKGROUND: The fat components of red meat products have been of interest to researchers due to the health aspects of excess fat consumption by humans. We hypothesized that differences in protein expression have an impact on adipose tissue formation during beef cattle development and growth. Therefore, in this study we evaluated the differences in the discernable proteome of subcutaneous adipose tissues of 35 beef crossbred steers [Charolais x Red Angus (CHAR) (n = 13) and Hereford x Angus (HEAN) (n = 22)] with different back fat (BF) thicknesses. The goal was to identify specific protein markers that could be associated with adipose tissue formation in beef cows. RESULTS: Approximately 541-580 protein spots were detected and compared in each crossbred group, and 33 and 36 protein spots showed expression differences between tissues with high and low BF thicknesses from HEAN and CHAR crossbed, respectively. The annexin 1 protein was highly expressed in both crossbred steers that had a higher BF thickness (p < 0.05) and this was further validated by a western blot analysis. In 13 tissues of CHAR animals and 22 tissues of HEAN animals, the relative expression of annexin 1 was significantly different (p < 0.05) between tissues with high and low BF thicknesses. CONCLUSION: The increased expression of annexin 1 protein has been found to be associated with higher BF thickness in both crossbred steers. This result lays the foundation for future studies to develop the protein marker for assessing animals with different BF thickness.

[Synthesis and antitumor activity of benzoic nitrogen mustard derivatives].

To study the effect of isoprenoid and aliphatic saturated alcohols as modificator on benzoic nitrogen mustard, the intermediate 4-[N,N-bis(2-chloroethyl) amino] benzoic acid 4 was prepared in four steps utilizing p-amino benzoic acid as the starting material. Target compounds were synthesized by the catalytic esterification of DCC/DMAP and the structures of the six new esters were characterized by elemental analysis, 1H NMR, 13C NMR and MS. Antitumor activities were evaluated in vitro using MTT assay. The result showed that some derivatives were more potent than the intermediate 4, and compound 5c modified with dodecanol exhibited similar activity to the commercial drug melphalan.

[Influence and mechanism of peroxisome proliferation activated receptor-alpha expression induced by WY14643 in rat lung with acute lung injury].

OBJECTIVE: To investigate the effect of WY14643 [peroxisome proliferation activated receptor-alpha (PPAR-alpha) activator, 4-cholro-6-(2.3-xylidino)-2-pyrimidinylthio acetic acid] on PPAR-alpha expression in lung of acute lung injury (ALI) induced by lipopolysaccharide (LPS) and its mechanism. METHODS: One hundred and four male Wistar rats were randomly divided into four groups: control group, ALI group, WY14643 1 mg group and WY14643 3 mg group. Wistar rats were given LPS (5 mg/kg) before intratracheal challenge with WY14643 (1 mg/kg and 3 mg/kg). Rats of all groups were sacrificed at 1, 2, 4, 8 hours after LPS challenge. The levels of PPAR-alpha mRNA in lung were measured by semi quantitative reverse transcription-polymerase chain reaction, the levels of PPAR-alpha protein in rats lung homogenate were measured by Western blot. RESULTS: The levels of PPAR-alpha mRNA at 2,4 and 8 hours in WY14643 1 mg group and WY14643 3 mg group were significantly higher than that in ALI group (P<0.05 or P<0.01). The levels of PPAR-alpha mRNA at all time in ALI group was significantly lower than that in control group (P<0.01). Meanwhile,the levels of PPAR-alpha protein at all time in WY14643 1 mg group and WY14643 3 mg group were significantly higher than that in ALI group (P<0.01). The level of PPAR-alpha mRNA at 4 hours and 8 hours in WY14643 1 mg group and at 2,4 and 8 hours in WY14643 3 mg group were significantly higher than those in control group too (P<0.05 or P<0.01). CONCLUSION: The expressions of PPAR-alpha mRNA and protein are all significantly low in the lung of rats with acute lung injury. WY14643 may upregulate the level of PPAR-alpha in the lung tissue in rats with acute lung injury.

Chemosensitizing multiple drug resistance of human carcinoma by Bicyclol involves attenuated p-glycoprotein, GST-P and Bcl-2.

Bicyclol, a second generation of synthetic hepatoprotectant being used in China for anti-hepatitis therapy, shows chemosensitizing effect on reverting multiple drug resistance (MDR) of cytostatic agents in two established MDR carcinoma cell lines, vincristine resistant human stomatic epidermoid carcinoma VinRKB and adriamycin resistant human breast carcinoma AdrRMCF-7. The reversal rate of drug resistance was calculated from the changes of the IC50 of cell growth inhibition. Bicyclol at the concentration of 25, 50, 100 microM induced 2.8 7.3 and 20.7 fold, respectively, reversal of vincristine resistance in VinRKB cell. Bicyclol also reversed the cross-resistance of VinRKB cell to taxol and AdrRMCF-7 cell resistance to adriamycin at the similar range of potency. Further, Bicyclol recovered the reduced accumulation of adriamycin in AdrRMCF-7 cell partially to the level in drug-sensitive MCF-7 cell, indicate the inhibition of MDR related membrane efflux pump system. Overexpression of membrane p-glycoprotein coded by Mdr-1 genes, the most common efflux pump correlated to MDR, was found in both VinRKB and AdrRMCF-7 cells by Western blot and immunocytochemistry as compared with drug-sensitive cells. The p-glycoprotein was decreased to the levels in drug-sensitive cells when VinRKB and AdrRMCF-7 cells were treated with Bicyclol for 12-72 hours. Both VinRKB and AdrRMCF-7 cells showed increased GSH contents, and AdrRMCF-7 cell showed increased GST activity and the overexpression of Bcl-2 protein, by which molecules are tightly related to the MDR formation besides Mdr-1 p-glycoprotein. Bicyclol reduced the GSH contents, GST activities and Bcl-2 expression. All these data demonstrate that, by modifying the expressions of Mdr-1, GSH/GST and Bcl-2, Bicyclol increases the intracellular drug concentration and sensitizes the resistant cells to the anti-carcinoma agents.