Insights into the Corrosion Inhibition Mechanism of Canavalia gladiata Leaf Extract for Copper in Sulfuric Acid Medium.

Canavalia gladiata leaf extract (CGLE) is extracted from crop waste employing a water decoction method. By employing electrochemical techniques, morphology analysis, quantum chemical calculations, and other methods, we extensively investigated the anticorrosion efficacy of CGLE on copper within a H2SO4 solution. The outcomes reveal that at 298 K, a CGLE concentration of 800 mg/L attains a remarkable inhibition efficiency (IE) of 96.8%. Additionally, we examined the impact of CGLE on the corrosion resistance of copper at varying temperatures. Even with rising temperatures, CGLE manages to sustain an IE of over 95%. This indicates that CGLE is mainly chemisorption based on the copper, leading to a strong adsorption. The surface test results show a noteworthy decrease in the extent of copper surface corrosion upon the introduction of CGLE. The study of the adsorption model demonstrates the alignment of CGLE adsorption onto the copper with the Langmuir adsorption.

Selection and identification of a prohibitin 2-binding DNA aptamer for tumor tissue imaging and targeted chemotherapy.

Tumor cell-targeting molecules play a vital role in cancer diagnosis, targeted therapy, and biomarker discovery. Aptamers are emerging as novel targeting molecules with unique advantages in cancer research. In this work, we have developed several DNA aptamers through cell-based systematic evolution of ligands by exponential enrichment (Cell-SELEX). The selected SYL-6 aptamer can bind to a variety of cancer cells with high signal. Tumor tissue imaging demonstrated that SYL-6-Cy5 fluorescent probe was able to recognize multiple clinical tumor tissues but not the normal tissues, which indicates great potential of SYL-6 for clinical tumor diagnosis. Meanwhile, we identified prohibitin 2 (PHB2) as the molecular target of SYL-6 using mass spectrometry, pull-down and RNA interference assays. Moreover, SYL-6 can be used as a delivery vehicle to carry with doxorubicin (Dox) chemotherapeutic agents for antitumor targeted chemotherapy. The constructed SYL-6-Dox can not only selectively kill tumor cells in vitro, but also inhibit tumor growth with reduced side effects in vivo. This work may provide a general tumor cell-targeting molecule and a potential biomarker for cancer diagnosis and targeted therapy.

Dihydroartemisinin inhibits the development of colorectal cancer by GSK-3ß/TCF7/MMP9 pathway and synergies with capecitabine.

Patients with colorectal cancer (CRC) suffer from poor prognosis and lack effective drugs. Dihydroartemisinin (DHA) has anti-cancer potential but the mechanism remains unclear. We elucidated the effects and mechanism of DHA on CRC development with the aim of providing an effective, low-toxicity drug and a novel strategy for CRC. Herein, proliferation assay, transwell assay, tube formation assay, metastasis models, PDX model and AOM/DSS model were used to reveal the effects of DHA on CRC. The key pathway and target were identified by RNA-seq, ChIP, molecular docking, pull down and dual-luciferase reporter assays. As a result, DHA showed a strong inhibitory effect on the growth, metastasis and angiogenesis of CRC with no obvious toxicity, and the inhibitory effect was similar to that of the clinical drug Capecitabine (Cap). Indeed, DHA directly targeted GSK-3ß to inhibit CRC development through the GSK-3ß/TCF7/MMP9 pathway. Meaningfully, DHA in combination with Cap enhanced the anti-cancer effect, and alleviated Cap-induced diarrhoea, immunosuppression and inflammation. In conclusion, DHA has the potential to be an effective and low-toxicity drug for the treatment of CRC. Furthermore, DHA in combination with Cap could be a novel therapeutic strategy for CRC with improved efficacy and reduced side effects.

Chiral Oxazaborolidinium Ion (COBI)-Catalyzed Reaction of Aldimine with Tributyltin Cyanide: Mechanism and Origin of Stereoselectivity.

By conducting density functional theory (DFT) calculations, the detailed reaction mechanisms of aldimines with tributyltin cyanide under the catalytic influence of chiral oxazaborolidinium ion (COBI) have been uncovered. Three potential reaction pathways were examined, and two stereoselective routes were determined for the most energetically favorable mechanism. In the primary route, a proton is transferred from the COBI catalyst to the aldimine substrate, which is then followed by the C-C bond formation to produce the final product. Subsequently, NBO analyses of the stereoselectivity-determining transition states were conducted to identify the crucial role of hydrogen bond interactions in controlling stereoselectivity. These computed findings should prove invaluable in comprehending the detailed mechanisms and underlying origins of stereoselectivity for COBI-mediated reactions of this type.

PGC-1α promotes colorectal carcinoma metastasis through regulating ABCA1 transcription.

Colorectal cancer (CRC) is a highly aggressive cancer in which metastasis plays a key role. However, the mechanisms underlying metastasis have not been fully elucidated. Peroxisome proliferator-activated receptor gamma coactivator 1α (PGC-1α), a regulator of mitochondrial function, has been reported as a complicated factor in cancer. In this study, we found that PGC-1α was highly expressed in CRC tissues and was positively correlated with lymph node and liver metastasis. Subsequently, PGC-1α knockdown was shown to inhibit CRC growth and metastasis in both in vitro and in vivo studies. Transcriptomic analysis revealed that PGC-1α regulated ATP-binding cassette transporter 1 (ABCA1) mediated cholesterol efflux. Mechanistically, PGC-1α interacted with YY1 to promote ABCA1 transcription, resulting in cholesterol efflux, which subsequently promoted CRC metastasis through epithelial-to-mesenchymal transition (EMT). In addition, the study identified the natural compound isoliquiritigenin (ISL) as an inhibitor that targeted ABCA1 and significantly reduced CRC metastasis induced by PGC-1α. Overall, this study sheds light on how PGC-1α promotes CRC metastasis by regulating ABCA1-mediated cholesterol efflux, providing a basis for further research to inhibit CRC metastasis.

Diosmetin suppresses the progression of ESCC by CDK2/Rb/E2F2/RRM2 pathway and synergies with cisplatin.

Cisplatin (CDDP) is the first-line drug in the clinical treatment of esophageal squamous cell carcinoma (ESCC), which has severe nephrotoxicity. Diosmetin (DIOS) can protect kidney from oxidative damage, however, its function in ESCC is unknown. This study aims to explore the effect and mechanism of DIOS on ESCC and its combined effect with CDDP. Herein, we found that DIOS significantly inhibited the progression of ESCC in vitro and in vivo. Furthermore, the anti-tumor effect of DIOS was not statistically different from that of CDDP. Mechanically, transcriptomics revealed that DIOS inhibited the E2F2/RRM2 signaling pathway. The transcriptional regulation of RRM2 by E2F2 was verified by luciferase assay. Moreover, docking model, CETSA, pull-down assay and CDK2 inhibitor assay confirmed that DIOS directly targeted CDK2, leading to significant suppression of ESCC. Additionally, the patient-derived xenografts (PDX) model showed that the combination of DIOS and CDDP significantly inhibited the growth of ESCC. Importantly, the combined treatment with DIOS and CDDP significantly reduced the mRNA expression levels of kidney injury biomarkers KIM-1 and NGAL in renal tissue, as well as the levels of blood urea nitrogen, serum creatinine and blood uric acid compared to the single treatment with CDDP. In conclusion, DIOS could be an effective drug and a potential chemotherapeutic adjuvant for ESCC treatment. Furthermore, DIOS could reduce the nephrotoxicity of CDDP to some extent.

Repurposed benzydamine targeting CDK2 suppresses the growth of esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is one of the leading causes of cancer death worldwide. It is urgent to develop new drugs to improve the prognosis of ESCC patients. Here, we found benzydamine, a locally acting non-steroidal anti-inflammatory drug, had potent cytotoxic effect on ESCC cells. Benzydamine could suppress ESCC proliferation in vivo and in vitro. In terms of mechanism, CDK2 was identified as a target of benzydamine by molecular docking, pull-down assay and in vitro kinase assay. Specifically, benzydamine inhibited the growth of ESCC cells by inhibiting CDK2 activity and affecting downstream phosphorylation of MCM2, c-Myc and Rb, resulting in cell cycle arrest. Our study illustrates that benzydamine inhibits the growth of ESCC cells by downregulating the CDK2 pathway.

DNA Aptamer Selected against Esophageal Squamous Cell Carcinoma for Tissue Imaging and Targeted Therapy with Integrin ß1 as a Molecular Target.

Esophageal cancer, especially esophageal squamous cell carcinoma (ESCC), poses a serious threat to human health. It is urgently needed to develop recognition tools and discover molecular targets for early diagnosis and targeted therapy of esophageal cancer. Here, we developed several DNA aptamers that can bind to ESCC KYSE410 cells with a nanomolar range of dissociation constants by using cell-based systematic evolution of ligands by exponential enrichment (cell-SELEX). The selected A2 aptamer is found to strongly bind with multiple cancer cells, including several ESCC cell lines. Tissue imaging displayed that the A2 aptamer can specifically recognize clinical ESCC tissues but not the adjacent tissues. Moreover, we identified integrin ß1 as the binding target of A2 through pull-down and RNA interference assays. Meanwhile, molecular docking and mutation assays suggested that A2 probably binds to integrin ß1 through the nucleotides of DA16-DG21, and competitive binding and structural alignment assays indicated that A2 shares the overlapped binding sites with laminin and arginine-glycine-aspartate ligands. Furthermore, we engineered A2-induced targeted therapy for ESCC. By constructing A2-tethered DNA nanoassemblies carrying multiple doxorubicin (Dox) molecules as antitumor agents, inhibition of tumor cell growth in vitro and in vivo was achieved. This work provides a useful targeting tool and a potential molecular target for cancer diagnosis and targeted therapy and is helpful for understanding the integrin mechanism and developing integrin inhibitors.

A Pan-cancer Analysis Reveals the Abnormal Expression and Drug Sensitivity of CSF1.

BACKGROUND: Colony-stimulating factor-1 (CSF1) is a cytokine that is closely related to normal organ growth and development as well as tumor progression. OBJECTIVE: We aimed to summarize and clarify the reasons for the abnormal expression of CSF1 in tumors and explore the role of CSF1 in tumor progression. Furthermore, drug response analysis could provide a reference for clinical medication. METHODS: The expression of CSF1 was analyzed by TCGA and CCLE. Besides, cBioPortal and MethSurv databases were used to conduct mutation and DNA methylation analyses. Further, correlations between CSF1 expression and tumor stage, survival, immune infiltration, drug sensitivity and enrichment analyses were validated via UALCAN, Kaplan-Meier plotter, TIMER, CTRP and Coexperia databases. RESULTS: CSF1 is expressed in a variety of tissues; meaningfully, it can be detected in the blood. Compared with normal tissues, CSF1 expression was significantly decreased in most tumors. The missense mutation and DNA methylation of CSF1 might cause the downregulated expression. Moreover, decreased CSF1 expression was related to higher tumor stage and worse survival. Further, the promoter DNA methylation level of CSF1 was prognostically significant in most tumors. Besides, CSF1 was closely related to immune infiltration, especially macrophages. Importantly, CSF1 expression was associated with a good response to VEGFRs inhibitors, which may be due to the possible involvement of CSF1 in tumor angiogenesis and metastasis processes. CONCLUSION: The abnormal expression of CSF1 could serve as a promising biomarker of tumor progression and prognosis in pan-cancer. Significantly, angiogenesis and metastasis inhibitors may show a good response to CSF1-related tumors.

Tegaserod Maleate Inhibits Esophageal Squamous Cell Carcinoma Proliferation by Suppressing the Peroxisome Pathway.

Esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC) are the two major types of esophageal cancer (EC). ESCC accounts for 90% of EC. Recurrence after primary treatment is the main reason for poor survival. Therefore, recurrence prevention is a promising strategy for extending the 5-year survival rate. Here, we found tegaserod maleate could inhibit ESCC proliferation both in vivo and in vitro. Proteomics analysis revealed that tegaserod maleate suppressed the peroxisome signaling pathway, in which the key molecules peroxisome membrane protein 11B (PEX11B) and peroxisome membrane protein 13 (PEX13) were downregulated. The immunofluorescence, catalase activity assay, and reactive oxygen species (ROS) confirmed that downregulation of these proteins was related to impaired peroxisome function. Furthermore, we found that PEX11B and PEX13 were highly expressed in ESCC, and knockout of PEX11B and PEX13 further demonstrated the antitumor effect of tegaserod maleate. Importantly, tegaserod maleate repressed ESCC tumor growth in a patient-derived xenograft (PDX) model in vivo. Our findings conclusively demonstrated that tegaserod maleate inhibits the proliferation of ESCC by suppressing the peroxisome pathway.

Evolution of DNA aptamers against esophageal squamous cell carcinoma using cell-SELEX.

Esophageal cancer is the ninth most common cancer and the sixth most common cause of cancer-related death worldwide, and the esophageal squamous cell carcinoma (ESCC) subtype accounts for about 90% of all cases of esophageal cancer globally. Currently, ESCC is usually diagnosed in late stages, and targeted therapy is lacking. Therefore, the development of ESCC-specific recognition molecules for an early detection and targeted treatment of ESCC is urgently needed. Aptamers are an excellent molecular recognition tool with unique advantages. In this manuscript, three aptamers (S2, S3, and S8) specific to ESCC cells were successfully screened via cell-SELEX. The experimental results displayed the high affinities of the three aptamers for target KYSE150 cells with dissociation constants in the nanomolar range. The specificity evaluation showed that S2 only bound target KYSE150 cells, but S3 and S8 were capable of targeting a series of ESCC cells. Moreover, several truncated aptamers were generated through sequence optimization. In particular, an ultrashort aptamer S3-2-3 with only 18 bases was successfully obtained; after labeling with Cy5 dyes, it was feasible for the specific imaging of ESCC tissues. Furthermore, the target types of the selected aptamers were preliminarily identified as membrane proteins, and target proteins could be captured by S3-2-3, which may be useful for biomarker discovery. Therefore, the selected aptamers hold great potential for clinical diagnosis, biomarker discovery, and the targeted therapy of ESCC.

DNA polymerase ß deficiency promotes the occurrence of esophageal precancerous lesions in mice.

Esophageal mucosa undergoes mild, moderate, severe dysplasia, and other precancerous lesions and eventually develops into carcinoma in situ, and understanding the developmental progress of esophageal precancerous lesions is beneficial to prevent them from developing into cancer. DNA polymerase ß (Polß), a crucial enzyme of the base excision repair system, plays an important role in repairing damaged DNA and maintaining genomic stability. Abnormal expression or deletion mutation of Polß is related to the occurrence of esophageal cancer, but the role of Polß deficiency in the esophageal precancerous lesions is still unclear. Here, esophageal mucosa Polß-knockout mice were used to explore the relationship of Polß deficiency with esophageal precancerous lesions. First, we found the degree and number of esophageal precancerous lesions in Polß-KO mice were more serious than those in Polß-Loxp mice after N-nitrosomethylbenzylamine (NMBA) treatment. Whole exome sequencing revealed that deletion of Polß increased the frequency of gene mutations. Gene expression prolife analysis showed that the expression of proteins correlated to cell proliferation and the cell cycle was elevated in Polß-KO mice. We also found that deletion of Polß promoted the proliferation and clone formation as well as accelerated cell cycle progression of human immortalized esophageal epithelial cell line SHEE treated with NMBA. Our findings indicate that Polß knockout promotes the occurrence of esophageal precancerous lesions.

p21-activated kinase 4 promotes the progression of esophageal squamous cell carcinoma by targeting LASP1.

Esophageal squamous cell carcinoma (ESCC) is one of the most common malignant tumors of the digestive tract in humans. Several studies have indicated that PAK4 is associated with the risk of ESCC and may be a potential druggable kinase for ESCC treatment. However, the underlying mechanism remains largely unknown. The aim of our study is to identify the functional role of PAK4 in ESCC. To determine the expression of PAK4 in ESCC, Western blot analysis and immunohistochemistry were performed, and the results showed that PAK4 is significantly upregulated in ESCC tissues and cell lines compared with normal controls and normal esophageal epithelial cell line. To further investigate the role of PAK4 in ESCC, cell viability assays, anchorage-independent cell growth assays, wound healing assays, cellular invasion assays, in vivo xenograft mouse models, and metastasis assays were conducted, and the results showed that PAK4 can significantly facilitate ESCC proliferation and metastasis in vitro and in vivo. To determine the potential target of PAK4 in ESCC progression, a pull-down assay was performed, and the results showed that LASP1 may be a potential target of PAK4. An immunoprecipitation assay and confocal microscopy analysis confirmed that PAK4 can bind to and colocalize with LASP1 in vitro and in cells. Notably, rescue experiments further illustrated the mechanistic network of PAK4/LASP1. Our research reveals the oncogenic roles of PAK4 in ESCC and preliminarily elucidates the mechanistic network of PAK4/LASP1 in ESCC.

Mefloquine Inhibits Esophageal Squamous Cell Carcinoma Tumor Growth by Inducing Mitochondrial Autophagy.

Esophageal squamous cell carcinoma (ESCC) has a worldwide impact on human health, due to its high incidence and mortality. Therefore, identifying compounds to increase patients' survival rate is urgently needed. Mefloquine (MQ) is an FDA-approved anti-malarial drug, which has been reported to inhibit cellular proliferation in several cancers. However, the anti-tumor activities of the drug have not yet been completely defined. In this study, mass spectrometry was employed to profile proteome changes in ESCC cells after MQ treatment. Sub-cellular localization and gene ontology term enrichment analysis suggested that MQ treatment mainly affect mitochondria. The KEGG pathway enrichment map of down-regulated pathways and Venn diagram indicated that all of the top five down regulated signaling pathways contain four key mitochondrial proteins (succinate dehydrogenase complex subunit C (SDHC), succinate dehydrogenase complex subunit D, mitochondrially encoded cytochrome c oxidase III and NADH: ubiquinone oxidoreductase subunit V3). Meanwhile, mitochondrial autophagy was observed in MQ-treated KYSE150 cells. More importantly, patient-derived xenograft mouse models of ESCC with SDHC high expression were more sensitive to MQ treatment than low SDHC-expressing xenografts. Taken together, mefloquine inhibits ESCC tumor growth by inducing mitochondrial autophagy and SDHC plays a vital role in MQ-induced anti-tumor effect on ESCC.

The Establishment of Esophageal Precancerous Lesion Model by Using p53 Conditional Knockout Mouse in Esophageal Epithelium.

Understanding the molecular mechanisms of precancerous lesion of esophageal cancer is beneficial for early diagnosis and early treatment. The deletion of p53 gene is common in esophageal cancer, but its pathogenesis is still unclear. An animal model is urgently needed to study the mechanisms of esophageal cancer and p53 deficiency. KO mice (p53flox/flox.ED-L2-Cre+/-) and the corresponding control Loxp mice (p53flox/flox.ED-L2-Cre-/-) were obtained by crossing between the p53flox/flox mice and ED-L2-Cre+/- mice. Methylbenzylnitrosamine (NMBA) was injected subcutaneously to induce esophageal precancerous lesion of these two groups of mice. Hematoxylin and eosin staining analysis was performed to evaluate the number and extent of esophageal precancerous lesions in KO mice and Loxp mice at the 16th and 48th weeks. Immunohistochemistry analysis was used to detect the change of Ki67, P21, Bcl-2, and Bax proteins. The number and extent of esophageal precancerous lesions in KO mice were significantly increased compared with the control at the 16th and 48th weeks under the induction of NMBA. The Ki67, P21, Bcl-2, and Bax proteins also had cancer-related pathological characteristics. These results suggest that the esophageal precancerous lesion model was established under the combined effect of p53 gene deletion in esophageal epithelium and NMBA, which could provide a new esophageal precancerous lesion model to explore the mechanism of precancerous lesions.

Correction to: TOPK promotes metastasis of esophageal squamous cell carcinoma by activating the Src/GSK3ß/STAT3 signaling pathway via γ-catenin.

Following publication of the original article [1], the authors reported the errors in Fig. 1C and D, Fig. 2, Fig. 4B and C and Fig. 6D and E.

Dihydroartemisinin Inhibits the Proliferation of Esophageal Squamous Cell Carcinoma Partially by Targeting AKT1 and p70S6K.

Dihydroartemisinin (DHA), a sesquiterpene lactone with endoperoxide bridge, is one of the derivatives of artemisinin. In addition to having good antimalarial properties, DHA exhibits anticancer effects including against malignant solid tumors. However, the mechanism by which DHA inhibits the progression of esophageal cancer, especially esophageal squamous cell carcinoma (ESCC), is unclear. In this study, DHA was found to inhibit the proliferation of ESCC, and the underlying molecular mechanisms were explored. DHA inhibited ESCC cells proliferation and anchorage-independent growth. Flow cytometry analysis revealed that DHA significantly blocked cell cycle in the G1 phase. The results of human phospho-kinase array revealed that DHA downregulated the levels of p70S6KT389 and p70S6KT421/S424. Furthermore, the levels of mTORS2448, p70S6KT389, p70S6KT421/S424 and RPS6S235/S236 were decreased after DHA treatment in KYSE30 and KYSE150 cells. We then explored the proteins targeted by DHA to inhibit the mTOR-p70S6K-RPS6 pathway. Results of the in vitro kinase assay revealed that DHA significantly inhibited phosphorylation of mTORS2448 by binding to AKT1 and p70S6K kinases. In vivo, DHA inhibited the tumor growth of ESCC patient-derived xenografts and weakened p-mTOR, p-p70S6K, and p-RPS6 expression in tumor tissues. Altogether, our results indicate that DHA has antiproliferative effects in ESCC cells and can downregulate mTOR cascade pathway partially by binding to AKT1 and p70S6K. Thus, DHA has considerable potential for the prevention or treatment of ESCC.

Ornithine decarboxylase inhibition downregulates multiple pathways involved in the formation of precancerous lesions of esophageal squamous cell cancer.

The high incidence and mortality of esophageal squamous cell cancer (ESCC) is a major health problem worldwide. Precancerous lesions of ESCC may either progress to cancer or revert to normal epithelium with appropriate interventions; the bidirectional instability of the precancerous lesions of ESCC provides opportunities for intervention. Reports suggest that the upregulation of ornithine decarboxylase (ODC) is closely related to carcinogenesis. In this study, we investigated whether ODC may act as a target for chemoprevention in ESCC. Immunohistochemistry (IHC) assays indicate that ODC expression is higher in esophageal precancerous lesions compared with normal tissue controls. Its overexpression promotes cell proliferation and transformation of normal esophageal epithelial cells, and its activity is increased after N-nitrosomethylbenzylamine (NMBA) induction in Shantou human embryonic esophageal cell line (SHEE) and human immortalized cells (Het1A) cells. In addition, p38 α, extracellular regulated kinase (ERK1/2) in the mitogen-activated protein kinase pathway and protein kinase B (AKT)/mammalian target of rapamycin (mTOR)/ribosomal protein S6 kinase (p70S6K) pathways are activated in response to NMBA treatment. Difluoromethylornithine (DFMO) is an ODC inhibitor, which inhibits NMBA-induced activation of p38 α, ERK1/2 and AKT/mTOR/p70S6K pathways; this has been verified by Western blotting. DFMO was also found to suppress the development of esophageal precancerous lesions in an NMBA-induced rat model; IHC demonstrated p38 α, ERK1/2, and AKT/mTOR/p70S6K pathways to be downregulated in these rats. These findings indicate the mechanisms by which ODC inhibition suppresses the development of esophageal precancerous lesions by downregulating p38 α, ERK1/2, and AKT/mTOR/p70S6k signaling pathways, ODC may be a potential target for chemoprevention in ESCC.

Proteome and phosphoproteome reveal mechanisms of action of atorvastatin against esophageal squamous cell carcinoma.

Statins comprise a class of prescription drugs used for reducing cholesterol. Evidence has also showed that statins could reduce cancer incidence. However, the anti-tumor mechanism of statins has not been fully defined. Here, we found that atorvastatin inhibited proliferation of esophageal squamous cell carcinoma (ESCC) cells. The underlying mechanisms were explored by mass spectrometry. The proteome data revealed that atorvastatin inhibited the cAMP and Rap1 signal pathways, except for Ras signal pathway. Interestingly, phosphoproteome profiles suggested that ERKT185/Y187, CDK1T14, and BRAC1S1189 phosphorylation-mediated Th17 cell differentiation, Gap junction and the Platinum drug resistance pathway were down-regulated after atorvastatin treatment. The phosphorylation levels of ERKT185/Y187, CDK1T14 and BRAC1S1189 were confirmed by western blotting in KYSE150 cells. More importantly, atorvastatin suppresses ESCC tumor growth in PDX models. The molecular changes in tumor tissues were confirmed by immunohistochemistry. In conclusion, deep-proteome and phosphoproteome analysis reveal a comprehensive mechanism that contributes to atorvastatin's anti-tumor effect.

Jie Du Tong Ye San Prevents N-Nitrosomethylbenzylamine-Induced Esophageal Carcinogenesis via Inhibition of Inflammation and Proliferation.

Jie du tong ye san (JDTYS), a traditional Chinese herbal formula, has been used for cancer adjuvant therapy in clinical use and has been shown to be effective in cancer patients. However, the mechanism of JDTYS is still unclear. Therefore, the aim of the present study is to investigate the chemopreventive effects of JDTYS for esophageal squamous cell carcinoma (ESCC) and to clarify the potential mechanism. N-nitrosomethylbenzylamine (NMBA)-induced rat esophageal carcinogenesis was used to evaluate the effect of JDTYS in vivo. Rats were treated with NMBA 3 times per week, for a total of 5 weeks. Rats in the treated groups were given JDTYS for 35 weeks. When rats were euthanized, esophageal tissue and blood were collected to evaluate the effects of JDTYS. The pathological grading of the rat esophageal preneoplastic lesions was classified and statistically analyzed. The protein levels of c-Jun and Ki67 were determined by immunohistochemistry. In addition, inflammation markers nuclear factor kappa B (NF-κB), cyclooxygenase-2 (COX-2), and the cluster of differentiation molecule 11B (CD11B) were also determined by immunohistochemistry. Moreover, the expression of COX-2 and Pentraxin 3 (PTX3) in rat serum was determined by enzyme-linked immunosorbent assay (ELISA). JDTYS could inhibit the formation of NMBA-induced esophageal preneoplastic lesions. JDTYS could downregulate the expression of proliferation related proteins Ki67 and c-Jun. Moreover, inflammation related proteins NF-κB, COX-2, and CD11B were inhibited and PTX3 was increased by JDTYS. In all, JDTYS is a promising chemopreventive formula against esophageal carcinogenesis by regulating inflammation and inhibiting cell proliferation.