Identification of Flavonoids from Scutellaria barbata D. Don as Inhibitors of HIV-1 and Cathepsin L Proteases and Their Structure-Activity Relationships.

Scutellaria barbata D. Don (SB, Chinese: Ban Zhi Lian), a well-known medicinal plant used in traditional Chinese medicine, is rich in flavonoids. It possesses antitumor, anti-inflammatory, and antiviral activities. In this study, we evaluated the inhibitory activities of SB extracts and its active components against HIV-1 protease (HIV-1 PR) and SARS-CoV2 viral cathepsin L protease (Cat L PR). UPLC/HRMS was used to identify and quantify the major active flavonoids in different SB extracts, and fluorescence resonance energy transfer (FRET) assays were used to determine HIV-1 PR and Cat L PR inhibitions and identify structure-activity relationships. Molecular docking was also performed, to explore the diversification in bonding patterns of the active flavonoids upon binding to the two PRs. Three SB extracts (SBW, SB30, and SB60) and nine flavonoids inhibited HIV-1 PR with an IC50 range from 0.006 to 0.83 mg/mL. Six of the flavonoids showed 10~37.6% inhibition of Cat L PR at a concentration of 0.1 mg/mL. The results showed that the introduction of the 4'-hydroxyl and 6-hydroxyl/methoxy groups was essential in the 5,6,7-trihydroxyl and 5,7,4'-trihydroxyl flavones, respectively, to enhance their dual anti-PR activities. Hence, the 5,6,7,4'-tetrahydroxyl flavone scutellarein (HIV-1 PR, IC50 = 0.068 mg/mL; Cat L PR, IC50 = 0.43 mg/mL) may serve as a lead compound to develop more effective dual protease inhibitors. The 5,7,3',4'-tetrahydroxyl flavone luteolin also showed a potent and selective inhibition of HIV-1 PR (IC50 = 0.039 mg/mL).

[Research Progress of Non-coding RNAs in the Regulation of Multiple Myeloma Bone Disease--Review].

Multiple myeloma bone disease is the most common complication of multiple myeloma, which mutually promotes the progression of multiple myeloma, severely affects patients' survival quality and prognosis. Recently, many studies revealed that non-coding RNAs play an important role in the imbalance of bone remodeling by regulating gene expression and participating in various signaling pathways. Additionally, most bone lesions fail to heal even when myeloma patients are in complete remission due to the sustained suppression of osteoblast activity, while non-coding RNAs may become a novel research field and clinical intervention targets. In this review, the latest research advances of non-coding RNAs which affect the occurrence and progress of multiple myeloma bone disease are summarized briefly.

[Research Progress of Non-coding RNA in Multiple Myeloma with Heart Disease---Review].

Some non-coding RNAs (ncRNA), as functional RNA molecules, lack potential to encode proteins, but can affect gene expression and disease progression through a variety of mechanisms. In multiple myeloma (MM), cardiovascular disease is one of the most common complications, which may be related to a variety of factors, including patient's own factors, disease-related factors, drug factors, etc. Non-coding RNA is considered to be an important regulator of cardiovascular event risk factors and cell function, and an important candidate target for improving the condition and prognostic assessment. This article briefly summarized the role of non-coding RNA in cardiac amyloidosis caused by MM, damage to the heart by inflammatory factors, and heart disease caused by chemotherapy drugs in recent years.

Asperochratides A-J, Ten new polyketides from the deep-sea-derived Aspergillus ochraceus.

Ten new C9 polyketides (asperochratides A-J, 1-10) and 14 known miscellaneous compounds (11-24) were isolated from the deep-sea-derived fungus Aspergillus ochraceus. Structures of the new compounds were elucidated by extensive spectroscopic analyses, modified Mosher's method, Mo2(OAc)4 induced circular dichroism (ICD) experiments, and ECD calculations. Structurally, compounds 1-11 and 16-18 share the same polyketide origin of the skeleton and belong to aspyrone co-metabolites. All isolates were tested for cytotoxic, anti-food allergic, anti-H1N1 virus, anti-microbe, and anti-inflammatory activities in vitro. Results showed that compounds 5-8 and 13-17 exerted significant cytotoxic effects on BV-2 cell line, and compound 16 showed the potential of anti-inflammatory activities.

An ethanol extract of the rhizome of Atractylodes chinensis exerts anti-gastritis activities and inhibits Akt/NF-κB signaling.

ETHNOPHARMACOLOGICAL RELEVANCE: The rhizome of Atractylodes chinensis (DC.) kodiz (Compositae) has traditionally been used to treat inflammatory disorders such as arthritis and stomach ache, but scanted report has been issued on its anti-inflammatory mechanisms. AIM OF THE STUDY: Here, we investigated the anti-gastritis activities and explored the mechanism of action of an ethanolic extract of the herb (Ac-EE). MATERIALS AND METHODS: Ac-EE was prepared with 95% ethanol. To determine its in vivo effects, we employed an HCl/EtOH-induced gastritis rat model. We used a lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage model for in vitro assays. Griess and MTT assays were used to measure nitric oxide (NO) production and cell viability, respectively. We used real-time PCR to determine mRNA levels. To measure prostaglandin E2 (PGE2) production we used a PGE2 EIA kit. To estimate protein levels and enzyme activities, we employed immunoblotting. Luciferase assays were used to examine nuclear transcription factor (NF)-κB activities. RESULTS: Intragastric administration of Ac-EE (30 mg/kg) ameliorated HCl/EtOH-induced stomach tissue damages in SD rats. Ac-EE inhibited the levels of NO and PGE2, down regulated mRNA and protein levels of inducible NO synthase (iNOS) and cyclooxygenase (COX)-2. Ac-EE suppressed the nuclear level of NF-κB (p50), and inhibited NF-κB luciferase activity. The Phosphorylation of Akt and IκBα was also inhibited by Ac-EE both in vivo and in vitro. CONCLUSION: Ac-EE treatment exerts an anti-gastritis effect in rats. Inhibition of the Akt/IκBα/NF-κB signaling pathway is associated with this effect, providing a pharmacological basis for the clinical application of the rhizome of A. chinensis in the treatment of inflammatory diseases.

In vitro assays suggest Shenqi Fuzheng Injection has the potential to alter melanoma immune microenvironment.

ETHNOPHARMACOLOGICAL RELEVANCE: A modern agent Shenqi Fuzheng Injection (SFI), prepared from Codonopsis Radix and Astragali Radix, has been commonly used as a supplementary therapy for cancers including melanoma. This agent was derived from a formula documented in the "National Collection of Chinese Medicine Prescriptions". The formula has long been used as a remedy for Qi deficiency that is closely associated with cancer-related fatigue and poor quality of life. However, the antimelanoma mechanisms of SFI remain unclear. Here we tested if SFI exerted antimelanoma effects by reprograming the tumour immune microenvironment using in vitro assays. MATERIALS AND METHODS: The cytotoxic activities of Jurkat T cells when co-cultured with A375 cells were determined in the presence or absence of SFI. The migratory activities of Jurkat T cells were examined in the transwell assay system. The mRNA expression and production of cytokines (IL-10, TGF ß and VEGF) in A375 cells in the presence or absence of SFI were determined by real-time PCR and ELISA, respectively. RESULTS: When A375 cells were co-cultured with Jurkat T cells in the presence of SFI (220µg/mL), a potent cytotoxicity effect against A375 cells was observed. Supernatants from A375 cells that were treated with SFI (110 and 220µg/mL) significantly increased the migratory capacity of Jurkat T cells in transwell assays. SFI also markedly reduced the mRNA expression levels and the release of immunosuppressive cytokines IL-10, TGF-ß and VEGF in A375 cells in a concentration-dependent manner. CONCLUSIONS: SFI enhanced the cytotoxic and migratory activities of Jurkat T cells towards A375 melanoma cells. The effects were associated with SFI's suppression on immunosuppressive cytokines for their release from and gene expressions in A375 melanoma cells. These in vitro findings suggested that SFI might reprogramme the immunosuppressive melanoma microenvironment in vivo to enhance the cytotoxicity of tumour-infiltrating immune cells. This study provides a pharmacological basis for the adjunctive use of SFI in melanoma treatment.

Liver fibrosis evaluation by ARFI and APRI in chronic hepatitis C.

AIM: To explore the value of liver fibrosis assessment by acoustic radiation force impulse (ARFI) and the AST/PLT ratio index (APRI) in chronic hepatitis C patients. METHODS: One hundred and twenty eight patients with chronic hepatitis C were examined using ARFI elastometry and APRI, calculated according to known formulae. The gold standard of liver biopsy was referred; ROC curve analysis was used to assess all ARFI and APRI values. The corresponding cut-off values, sensitivities, and specificities were calculated and compared. In addition, the correlation of liver fibrosis stages in chronic hepatitis C patients with ARFI measurements and APRI were also tested to evaluate significant data. RESULTS: The values of ARFI in S1-S4 were 1.23 ± 0.34 m/s, 1.48 ± 0.43 m/s, 2.06 ± 0.45 m/s, and 2.30 ± 0.87 m/s. The values of APRI in S1-S4 were 0.31 ± 0.45 m/s, 0.28 ± 0.38 m/s, 0.58 ± 0.59 m/s and 0.65 ± 0.34 m/s. ARFI (r = 0.649, P < 0.05) showed a better correlation with liver fibrosis stages in chronic hepatitis C than APRI (r = 0.478, P < 0.05). The areas under the ROC curves for ARFI and APRI were 0.775 and 0.721 for stages ≥ S2, 0.901 and 0.787 for stages ≥ S3, and 0.792 and 0.780 for S = 4, respectively. CONCLUSION: Both ARFI and APRI could evaluate liver fibrosis stages in chronic hepatitis C. ARFI is more accurate than the APRI index.

Chemical constituents of Abies delavayi.

Systematic phytochemical investigations on Abies delavayi afforded 110 compounds, including 49 terpenoids, 13 lignans, 20 flavonoids, three coumarins, and 25 other chemical constituents. By detailed analysis of one- and two-dimensional NMR spectroscopic and high-resolution mass spectrometric data, 10 previously unreported compounds were identified: they comprised three sesquiterpenoids, two diterpenoids, one triterpenoid, one monoterpenoid, one flavonoid, and two phenols. These 10 compounds and some previously known ones were subjected to two cytotoxic bioassays against three human tumor cell lines and NO production inhibition on RAW264.7 macrophages, respectively. (25R)-24,25-Dihydroabieslactone had the strongest cytotoxic activity against Colo-205 cells with an IC50 value of 19.0±3.7µg/mL. (+)-T-cadinol, 8,11,13-abietatrien-15-ol-18-yl acetate, 18-acetoxy-13-epi-manool, imperatorin, bergapten, and 5,7-O-dimethyl poriol exhibited weak inhibitory activity against LPS-induced NO production in RAW264.7 macrophages with IC50 values of approximately 50µg/mL.

Pseudonocardia antitumoralis sp. nov., a deoxynyboquinone-producing actinomycete isolated from a deep-sea sediment.

An aerobic actinomycete, designated SCSIO 01299(T), was isolated from a deep-sea sediment collected from the northern South China Sea at a depth of 3258 m. The isolate was found to be a natural producer of the synthesized antitumour agent deoxynyboquinone and its three new derivatives, pseudonocardians A, B and C. A blast search based on almost-complete 16S rRNA gene sequences showed that strain SCSIO 01299(T) had high sequence similarities with members of the genus Pseudonocardia. The 16S rRNA gene sequence phylogenetic tree revealed that strain SCSIO 01299(T) was a member of the genus Pseudonocardia. Phenotypic analysis, chemotaxonomy and DNA-DNA relatedness could readily distinguish the isolate from established members in this genus. It was concluded that strain SCSIO 01299(T) represents a novel species, for which the name Pseudonocardia antitumoralis sp. nov. is proposed. The type strain is SCSIO 01299(T) ( = DSM 45322(T)  = CCTCC M 2011255(T)).

Mono- and sesquiterpenoids, flavonoids, lignans, and other miscellaneous compounds of Abies georgei.

A systematic phytochemical investigation of the aerial parts of Abies georgei yielded nine new and 72 known compounds, including four monoterpenes, four sesquiterpenes, 25 flavonones, 14 lignans, and 34 other chemical constituents. The new compounds included two monoterpenes (1 and 2), two sesquiterpenes (3 and 4), three flavonones (5, 6, and 7), and two other components (8 and 9). Their chemical structures were established on the basis of various spectroscopic data. All the isolates were tested for antitumor and anti-inflammatory activities. The new compound 9,4'-dihydroxy-5,7-dimethoxy-8-methylchalcone (7) demonstrated a moderate antiproliferative effect on QGY-7703 tumor cells (IC (50)  = 17.6 µg/mL). The known compound isoferulaldehyde (67) exhibited the strongest inhibitory activity against lipopolysaccharide (LPS)-induced NO production in RAW 264.7 macrophages (IC (50) = 19.0 µg/mL). Abies georgei may be a significant source of beneficial pharmaceutical compounds.

[The comparative study of quartz dust and bleomycin-induced pulmonary fibrosis in rats].

OBJECTIVE: To compare the pulmonary alveolitis and the early fibrosis of pulmonary fibrosis induced by quartz dust and bleomycin in rats, and investigate their mechanism. METHODS: The female rats were divided into three groups: control group exposed to normal saline by the trachea; SiO2 group exposed to SiO2 by the trachea; BLM group exposed to BLM A5 by the trachea. Each half of the animals were sacrificed on the 7th and 14th day after exposure. The lungs of rats were collected to observe pulmonary alveolitis by HE staining and to observe fibrosis by saturated picric acid sirius red staining. The expression of tumor necrosis factor-alpha (TNF-alpha) and CD68 in pulmonary tissues were analyzed quantitatively by immunohistochemistry and image analysis system. RESULTS: (1) The alveolitis and pulmonary fibrosis of rats in both SiO2 group and BLM group were became more serious gradually over time, HE staining under light microscope showed that BLM group on the 7th day had the most obvious alveolitis (2.814 +/- 0.832), the saturated picric acid sirius red staining under polarized light showed that BLM group on the 14th day had the worst pulmonary fibrosis (1284.57 +/- 554.72), which were significantly higher than those (103.69 +/- 18.29 and 111.78 +/- 37.45) in control group and SiO2 group on the 7th day (P < 0.05). (2) The results of immunohistochemistry examination indicated that the expression (17.100 +/- 1.831) of TNF-alpha in the BLM group on the 7th day was significantly higher than those (0.451 +/- 0.441, 7.909 +/- 1.275 and 13.506 +/- 1.454) in control group, SiO2 group on 7th day and BLM group on 14th day (P < 0.05). The expression (22.778 +/- 2.512) of TNF-alpha in the SiO2 group on the 14th day was significantly higher than those in control group, SiO2 group on 7th day and BLM group on 14th day (P < 0.05). The expression (134.941 +/- 35.951) of CD68 in the SiO2 group on the 14th day was significantly higher than those in control group, SiO2 group on 7th day and BLM group on 14th day (P < 0.05). CONCLUSION: The early alveolitis of BLM-induced lung injury model was more serious than that of SiO2-induced lung injury model, and the fibrosis process of BLM-induced lung injury model was earlier than that of SiO2-induced lung injury model. TNF-alpha plays an important role in the course of both models, but macrophages is involved in SiO2-induced pulmonary in a more continuous way than in BLM-induced pulmonary fibrosis.

Systematic phytochemical investigation of Abies spectabilis.

Systematical phytochemical investigations on Abies spectabilis afforded 72 chemical constituents. On the basis of physical and spectroscopic data, including 1D and 2D homo- and heteronuclear NMR experiments (heteronuclear single quantum coherence (HSQC), (1)H-(1)H correlation spectroscopy (COSY), heteronuclear multiple bond connectivity (HMBC), and nuclear Overhauser effect spectroscopy (NOESY)), and by comparison with the literature references, they were identified as 3 triterpenoids, 23 diterpenoids, 1 sesquiterpenoid, 13 flavonoids, 12 lignans, and 20 other components. Among these compounds, three were identified as new including abieta-7,13-diene-12α-methoxy-18-oic acid (1), 7α-methoxy-dehydroabietic acid (2), and 5-hydroxy-6-methyl-7,4'-dimethoxyflavone-8-O-ß-D-glucopyranoside (3). These three new compounds (1-3) and all the known terpenoids (4-28) were tested for cytotoxic activities against four tumor cell lines: A549, COLO-25, QGY-25, and THP-1. However, none of them showed a positive effect (IC50>100 µM).

Abiesatrines A-J: anti-inflammatory and antitumor triterpenoids from Abies georgei Orr.

A novel spiro-lanostane (abiesatrine A, 1) was isolated from the aerial parts of Abies georgei together with 9 new (abiesatrines B-J, 2-10) and 10 known triterpenes (11-20). The new structures were established by the extensive analysis of their spectroscopic data. The configuration of 1, featuring a unique spirolactone formed by C-13 and C-23 via oxygen-bridge, was confirmed by X-ray crystallography, and its biopathway was tentatively proposed. Among these isolates, compound 16 showed the strongest inhibitory activity against LPS-induced NO production in RAW264.7 macrophages (IC(50) = 8.9 microg mL(-1)). While compounds 1 and 20 exhibited potent anti-proliferative effects on QGY-7703 cells with IC(50) values of 9.3 and 7.6 microg mL(-1), respectively. Preliminary structure-activity relationship (SAR) investigations defined structural feature of the 24Z-olefinic bond key to the lanostane and cycloartane pharmacophore.

Expression and significance of tumor drug resistance related proteins and beta-catenin in esophageal squamous cell carcinoma.

BACKGROUND AND OBJECTIVE: As chemotherapy is generally used in the clinical treatment of cancer, the problem of multidrug resistance (MDR) of tumors against the chemotherapeutic agents becomes more and more serious. It has been the major cause for the failure of the chemotherapy. We detected the expressions of beta-catenin and tumor drug resistance related proteins, MRP2, P-gp, and Bcl-2, in esophageal squamous cell carcinoma (ESCC) to explore their function and correlation in the occurrence and development of MDR in ESCC. METHODS: We used the tissue microarray technique, immunohistochemistry, and image analysis methods to detect the expressions of MRP2, P-gp, beta-catenin, and Bcl-2 proteins and analyze their relationships with clinical data in a ESCC tissue microarray consisting of 582 specimens of ESCC, 294 specimens of normal mucosa, 92 specimens of basal cell hyperplasia, and 87 specimens of dysplasia adjacent to cancer tissue. RESULTS: The integral optical density (IOD) of MRP2 and Bcl-2, which was 195.7 +/- 175.9 x 10(3)) and 90.5 +/- 112.5 x 10(3)), respectively, was significantly higher in ESCC than in normal mucosa, which was 104.8 +/- 86.1 x103) and 25.2 +/- 46.6 x 10(3)), respectively (P < 0.01). The IOD of P-gp and beta-catenin, which was 57.7 +/- 75.5 x 10(3)) and 32.0 +/- 47.0 x 10(3)) respectively, was significantly lower in ESCC than in normal mucosa, which was 114.8 +/- 106.6 x 10(3)) and 46.1 +/- 35.7 x 10(3)), respectively (P < 0.01). According to the following order, well differentiated moderately differentiated poorly differentiated, the IOD of MRP2 increased in ESCC (P < 0.01). The IOD of beta-catenin was higher in poorly differentiated ESCC than in well or moderately differentiated ESCC (P < 0.01). The IOD of Bcl-2 was lower in well differentiated ESCC than in poorly and moderately differentiated ESCC (P < 0.01). The IOD of beta-catenin and Bcl-2 was higher in the ESCC of specimens with infiltration depths that were in membrane mucosa than those in the muscular layer or serous coat (P < 0.01). The IOD of Bcl-2 was significantly higher in cases with lymph node metastasis than in cases without (P < 0.01). Positive correlations which were respectively between the expressions of P-gp and MRP2, the expressions of P-gp and Bcl-2 were found (r = 0.288 and r = 0.253, respectively, P < 0.01). CONCLUSIONS: MRP2, P-gp, and Bcl-2 may be taken as prognostic factors for MDR of ESCC. beta-catenin may play an important role in carcinogenesis and progression of ESCC.

Isolation, structure, and bioactivities of abiesadines A-Y, 25 new diterpenes from Abies georgei Orr.

Twenty-five new (abiesadines A-Y, 1-25) and 29 known (26-54) diterpenes were isolated from the aerial parts of Abies georgei. Abiesadine A (1) is a novel 8,14-seco-abietane, while abiesadine B (2) is a novel 9,10-seco-abietane. The structures of the new compounds were established on the basis of spectroscopic data analysis. Manool (52) showed the strongest effect against LPS-induced NO production in RAW264.7 macrophages with the IC(50) value of 11.0microg/mL. In another anti-inflammatory assay against TNFalpha-triggered NF-kappaB activity, (12R,13R)-8,12-epoxy-14-labden-13-ol (54) exhibited the strongest effect (IC(50)=8.7microg/mL). For antitumor assays, pomiferin A (26) and 8,11,13-abietatriene-7alpha,18-diol (29) both showed the most significant activity against LOVO cells (IC(50)=9.2microg/mL). While 7-oxocallitrisic acid (46) exhibited significant cytotoxicity against QGY-7703 tumor cells (IC(50)=10.2microg/mL).

Chemical constituents of Dracocephalum forrestii.

A systematic phytochemical examination of the whole plant Dracocephalum forrestii led to the isolation of 4 new and 65 known chemical constituents. By detailed 1D and 2D NMR spectroscopic analyses, the new compounds were identified as 4-hydroxy-3-methoxyphenylethanol 8- O-[(6- O-syringoyl)- beta- D-glucopyranoside] (1), 3,4,5-trimethoxyphenylethanol beta- D-glucopyranoside ( 2), 4- O-[ beta- D-glucopyranosyl-(1 --> 3)- alpha- L-rhamnopyranosyl]phenylethylcinnamamide (3), and 9''- O- N-butyl lithospermate (4). The new isolates were evaluated for inhibitory activities against LPS-induced NO production in RAW 264.7 macrophages. Compound 2 revealed a moderate effect without any cytotoxicity under the assayed concentrations.

Two new spirobiflavonoids from Abies chensiensis with moderate NO production inhibitory activity.

Phytochemical investigation of the aerial parts of Abies chensiensis afforded two new (compounds 2 and 3) and 27 known compounds, including the related compound larixinol ( 1). The structures of spirobiflavonoids 1- 3 were established using 1D and 2D NMR spectroscopic techniques. In addition, the structure of larixinol ( 1) was confirmed by X-ray crystallographic analysis. Compounds 1- 3 were evaluated for inhibitory activities against LPS-induced NO production in macrophages. Larixinol ( 1) showed moderate effects, with an IC(50) value of 60.0 microg/mL. In addition, it did not show any cytotoxicity on RAW 264.7 macrophages at 100 microg/mL.

Terpenoid constituents of Abies chensiensis with potential anti-inflammatory activity.

Six new triterpenes (neoabieslactones A-F, 1-6) and 17 known compounds were isolated from the aerial parts of Abies chensiensis. The structures of the new triterpenes were proposed by 1D and 2D NMR spectroscopy. Compound 1 was confirmed structurally by X-ray crystallography. In a bioassay against LPS-induced NO production in RAW264.7 macrophages, three compounds, neoabieslactone E (5), (12R,13R)-8,12-epoxy-14-labden-13-ol (7), and manool (8), exhibited IC(50) values of 9.1, 1.9, and 9.6 microg/mL, respectively.

Expression and significance of adenomatous polyposis coli, beta-catenin, E-cadherin and cyclin D1 in esophageal squamous cell carcinoma assessed by tissue microarray.

BACKGROUND AND OBJECTIVE: The genesis of esophageal squamous cell carcinoma(ESCC)is a multifactor and multistage process, in which Wnt signaling transduction pathway plays an important role in tumorigenesis and tumor progression. This study was to investigate the roles of four proteins in the Wnt pathway in tumorigenesis of ESCC, and their significances in the early diagnosis of ESCC. METHODS: The expression of adenomatous polyposis coli (APC), beta-catenin, E-cadherin and cyclinD1 was detected by immunohistochemistry using tissue microarrays consisting of 199 specimens of ESCC, 164 specimens of normal mucosa, 34 specimens of basal cell hyperplasia and 30 specimens of dysplasia adjacent to cancer tissues. RESULTS: The positive rates of APC and E-cadherin in ESCC were lower than those in the normal group (69.6% vs. 98.0%, p < 0.01; 19.6% vs. 96.3%, p < 0.01). The abnormal expression rates of beta-catenin and cyclin D1 in ESCC were higher than those in the normal group (65.5% vs. 1.2%,p < 0.01; 70.9% vs. 0.8%, p < 0.01). In accordance with the following order, normal epithelia --> basal cell hyperplasia --> dysplasia --> ESCC, hypoexpression of APC proteins occurred in ESCC, abnormalities of beta-catenin and E-cadherin started to appear in dysplasia, and overexpression of Cyclin D1 emerged from basal cell hyperplasia. From well to poorly differentiated ESCC, the expression of APC, E-cadherin and cyclin D1 were gradually reduced, while beta-catenin was increased. The expression of beta-catenin was not correlated with APC (r = -0.10, p > 0.05), was negatively correlated with E-cadherin (r = -0.31,p < 0.01) and positively correlated with cyclin D1(r = 0.49, p < 0.01). CONCLUSION: APC, E-cadherin, beta-catenin and cyclin D1 may play important roles in tumorigenesis of ESCC. Therefore, detection of E-cadherin, beta-catenin and cyclin D1 proteins may be helpful for the early diagnosis of ESCC.