ASB6 as an Independent Prognostic Biomarker for Colorectal Cancer Progression Involves Lymphatic Invasion and Immune Infiltration.

Background: ASB6, an E3 ubiquitin ligase, mediates the proteasomal degradation of its substrate proteins via the ubiquitin-proteasome pathway. ASB6 has been reported to play significant roles in several biological processes, including tumor stemness and endoplasmic reticulum stress. However, the underlying role and mechanism of ASB6 in colorectal cancer, particularly its association with immune infiltration levels and its prognostic significance, remain to be fully elucidated. Methods: We identified key prognostic genes in CRC patients through LASSO-penalized Cox regression, Univariate and Multivariate Cox regression analyses. Subsequently, we comprehensively analyzed the prognostic value of hub genes and constructed a prognostic nomogram. Finally, we identified ASB6 interacting proteins through immunoprecipitation-mass spectrometry (IP-MS) and constructed protein-protein interaction (PPI) networks and performed pathway enrichment analysis to explore the potential mechanisms of ASB6. Meanwhile, we evaluated the functions of ASB6 in CRC cells through in vitro cell experiments. Results: We identified ASB6 as a hub gene in CRC. ASB6 was highly expressed in CRC, and patients with high ASB6 expression had worse Disease-Free Interval (DFI), Disease-Specific Survival (DSS), Overall Survival (OS), and Progression-Free Interval (PFI). Correlation analysis showed that ASB6 expression were positively correlated with lymph node invasion and distal metastasis. Overexpression of ASB6 enhanced the migration ability of CRC cells. Multivariate Cox regression analysis revealed that ASB6 was an independent prognostic factor for OS and DSS in CRC. The nomogram model constructed based on multivariate analysis results had good predictive effects, with C-indexes of 0.811 and 0.934 for OS and DSS, respectively. Furthermore, analysis of immune infiltration levels showed that ASB6 expression were positively correlated with M2-type macrophage infiltration levels in CRC, and patients with high levels of both ASB6 and M2-type macrophages had a worse prognosis. Furthermore, pathway enrichment analysis of ASB6 interacting proteins identified by IP-MS suggested that ASB6 may play a crucial role through the response to unfolded protein pathway and protein processing in the endoplasmic reticulum pathway. Conclusions: ASB6 is significantly upregulated in CRC tissues and is a risk factor for prognosis in CRC patients. ASB6 enhances the migration ability of CRC cells. Therefore, ASB6 may be an independent prognostic biomarker and potential therapeutic target for CRC patients.

Characterization of risks and pathogenesis of respiratory diseases caused by rural atmospheric PM2.5.

Forty-six percent of the world's population resides in rural areas, the majority of whom belong to vulnerable groups. They mainly use cheap solid fuels for cooking and heating, which release a large amount of PM2.5 and cause adverse effects to human health. PM2.5 exhibits urban-rural differences in its health risk to the respiratory system. However, the majority of research on this issue has focused on respiratory diseases induced by atmospheric PM2.5 in urban areas, while rural areas have been ignored for a long time, especially the pathogenesis of respiratory diseases. This is not helpful for promoting environmental equity to aid vulnerable groups under PM2.5 pollution. Thus, this study focuses on rural atmospheric PM2.5 in terms of its chemical components, toxicological effects, respiratory disease types, and pathogenesis, represented by PM2.5 from rural areas in the Sichuan Basin, China (Rural SC-PM2.5). In this study, organic carbon is the most significant component of Rural SC-PM2.5. Rural SC-PM2.5 significantly induces cytotoxicity, oxidative stress, and inflammatory response. Based on multiomics, bioinformatics, and molecular biology, Rural SC-PM2.5 inhibits ribonucleotide reductase regulatory subunit M2 (RRM2) to disrupt the cell cycle, impede DNA replication, and ultimately inhibit lung cell proliferation. Furthermore, this study supplements and supports the epidemic investigation. Through an analysis of the transcriptome and human disease database, it is found that Rural SC-PM2.5 may mainly involve pulmonary hypertension, sarcoidosis, and interstitial lung diseases; in particular, congenital diseases may be ignored by epidemiological surveys in rural areas, including tracheoesophageal fistula, submucous cleft of the hard palate, and congenital hypoplasia of the lung. This study contributes to a greater scientific understanding of the health risks posed by rural PM2.5, elucidates the pathogenesis of respiratory diseases, clarifies the types of respiratory diseases, and promotes environmental equity.

Erratum: Efficacy of Shikonin against Esophageal Cancer Cells and its possible mechanisms in vitro and in vivo: Erratum.

[This corrects the article DOI: 10.7150/jca.21224.].

Nrf3 alleviates oxidative stress and promotes the survival of colon cancer cells by activating AKT/BCL-2 signal pathway.

Oxidative stress is closely linked to tumor initiation and development, conferring a survival advantage to cancer cells. Therefore, understanding cancer cells' antioxidant molecular mechanisms is crucial to cancer therapy. In this study, we discovered that H2O2-induced oxidative stress increased Nrf3 expression in colon cancer cells. Overexpression of Nrf3 decreased H2O2-mediated cytotoxicity and apoptosis. Furthermore, Nrf3 reduced reactive oxygen species levels and malondialdehyde concentrations after H2O2 treatment. Mechanistically, H2O2-mediated cell apoptosis involves multiple signaling proteins, including Akt, bcl-2, JNK, and p38. An increase in Nrf3 expression in colon cancer cells treated with H2O2 partly reversed Akt/Bcl-2 inhibition, whereas it decreased activation of p38 and JNK. In addition, we found that increasing Nrf3 decreased stress-associated chemical-induced cell death, resulting in drug resistance. According to these results, Nrf3 is critical for drug resistance and oxidant adaptation.

Nrf3 promotes the proliferation and migration of triple­negative breast cancer by activating PI3K/AKT/mTOR and epithelial­mesenchymal transition.

Nuclear factor erythroid 2-related factor 3 (Nrf3) is increasingly implicated in multiple types of cancer; however, its function in triple-negative breast cancer (TNBC) remains unclear. This study aimed to examine the role of Nrf3 in TNBC. Compared with adjacent normal tissues, TNBC tissues expressed higher levels of Nrf3, and its expression was negatively correlated with survival time. Additionally, Nrf3 knockdown reduced the proliferation and migration of TNBC cells, whereas overexpression of Nrf3 had the opposite effects in vitro and in vivo. Moreover, functional enrichment of TNBC cells overexpressing Nrf3 allowed for the identification of numerous genes and pathways that were altered following Nrf3 overexpression. Further study showed that overexpression of Nrf3 activated the PI3K/AKT/mTOR signaling pathway and regulated the expression of proteins associated with epithelial-mesenchymal transition. Nrf3 was found to directly bind to p110α promoter regions, as evidenced by luciferase reporter and chromatin immunoprecipitation assays. Furthermore, PI3K inhibitors partially decreased the proliferation and migration of the Nrf3 overexpressing TNBC cells. In conclusion, Nrf3 enhances cellular proliferation and migration by activating PI3K/AKT/mTOR signaling pathways, highlighting a novel therapeutic target for TNBC.

LINC01305 recruits basonuclin 1 to act on G-protein pathway suppressor 1 to promote esophageal squamous cell carcinoma.

EsophageaL squamous cell carcinoma (ESCC) is one of the most common and lethal tumors, however, its underlying molecular mechanisms are not completely understood and new therapeutic targets are needed. Here, we found that the transcription factor basonuclin 1 (BNC1) was significantly upregulated and closely related to the differentiation and metastasis of ESCC. Furthermore, BNC1, LINC01305, and G-protein pathway suppressor 1 (GPS1) had significant oncogenic roles in ESCC. In addition, in vivo experiments showed that knockdown of BNC1 indeed significantly inhibited the proliferation and metastasis of ESCC. We also revealed the molecular mechanism by which LINC01305 recruits BNC1 to the promoter of GPS1, and then GPS1 could mediate the JNK signaling pathway to promote the proliferation and metastases of ESCC. Taken together, we discovered the novel molecular mechanism by which LINC01305/BNC1 upregulates GPS1 expression to promote the development of ESCC, providing a new therapeutic target for ESCC.

Label-Free, Reusable, Equipment-Free, and Visual Detection of Hydrogen Sulfide Using a Colorimetric and Fluorescent Dual-Mode Sensing Platform.

In this work, we have found for the first time that the fluorescence of rhodamine B (RhB) would be dramatically reduced after it bound to hemin/G-quadruplex and reacted with •OH. Based on this finding, we have designed a colorimetric and fluorescent dual-mode sensing platform for visual detection of hydrogen sulfide (H2S). The constructed sensor is based on the formation of dsDNA and the G-quadruplex structure by the cytosine-Ag+-cytosine mismatch, causing H2O2-mediated catalysis to oxidize ABTS or RhB to induce a colorimetric or fluorescent change. In the presence of H2S, the solution color for colorimetric and fluorescent assays would change from dark green to pink and from green (fluorescence off) to bright yellow (fluorescence on), respectively. This dual-mode assay showed high selectivity toward H2S over other interference materials with a low measurable detection limit value (below than 2.5 µM), and it has been successfully applied to H2S visual detection in real samples. Moreover, the dual-mode sensing strategy presented an excellent reutilization character both in colorimetric and fluorescent assays. This method was employed as a label-free, simple, fast, and equipment-free platform for H2S detection with high selectivity and reusability. This work realized naked-eye detection both in colorimetric and fluorescent analysis at a lower concentration of H2S, demonstrating a promising strategy for on-site visual detection of H2S.

Analgesic tolerance and cross-tolerance to the bifunctional opioid/neuropeptide FF receptors agonist EN-9 and µ-opioid receptor ligands at the supraspinal level in mice.

The chimeric peptide EN-9 was reported as a κ-opioid/neuropeptide FF receptors bifunctional agonist that modulated chronic pain with no tolerance. Many lines of evidence have shown that the effect of the κ-opioid receptor is mediated by not only its specific activation but also downstream events participation, especially interaction with the µ-opioid receptor pathway in antinociception and tolerance on most occasions. The present study investigated the acute and chronic cross-tolerance of EN-9 with µ-opioid receptor agonist EM-2, DAMGO, and morphine after intracerebroventricularly (i.c.v) injection in the mouse tail-flick test. In the acute tolerance test, EN-9 showed symmetrical acute cross-tolerance to DAMGO but no cross-tolerance to EM2. In the chronic tolerance test, EN-9 had no tolerance after eight days of repeated administration. However, EN-9 illustrated complete cross-tolerance to morphine and symmetrical cross-tolerance to EM2. In addition, inhibition of NPFF receptor could induce the tolerance development of EN-9. These findings indicated that supraspinal EN-9-induced antinociception contains additional components, which are mediated by the downstream µ-opioid receptor pathway both in acute and chronic treatment, whereas the subtypes of µ-opioid receptor or NPFF system pathway involved in antinociceptive effects induced by EN-9 are complex. Identifying the receptor mechanism could help design preferable bifunctional opioid compounds.

Visual detection of aflatoxin B1 and zearalenone via activating a new catalytic reaction of "naked" DNAzyme.

Here, we have found for the first time that the catalytic activity of "naked" DNAzyme, a single-stranded G-quadruplex DNAzyme (S.DNAzyme), can be modulated by aflatoxin B1 (AFB1) and zearalenone (ZEN). In fact, S.DNAzyme can mimic the activity of horseradish peroxidase to perform oxidation of 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) to colored ABTS˙+ (dark green). This catalytic activity can be inhibited upon addition of AFB1, leading to color fade of the solution. But with ZEN, the solution color will change to a yellowish-brown or yellow color. Thus, we have exploited this finding to achieve label-free, naked-eye detection of AFB1 or ZEN, and have explored the possible detection mechanisms. This approach is able to detect AFB1 and ZEN concentrations as low as 0.18 µM and 0.29 µM, respectively. Even in real samples, the limit of detection values of these two analytes are lower than 3 µM. Notably, S.DNAzyme cross-reacted with three other tested aflatoxins, including aflatoxin B2, aflatoxin G1 and aflatoxin M1, revealing the potential for a broadly applicable method to identify the family of aflatoxins. The AFB1- or ZEN-triggered new catalytic reaction between "naked" DNAzyme and ABTS may offer new opportunities for on-site visual detection of mycotoxins.

Serum proteomics unveil characteristic protein diagnostic biomarkers and signaling pathways in patients with esophageal squamous cell carcinoma.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a common digestive tract malignant tumor with high incidence and dismal prognosis worldwide. However, the reliable biomarkers for clinical diagnosis and the underlying signaling pathways insights of ESCC are not unequivocally understood yet. The serum proteome may provide valuable clues for the early diagnosis of ESCC and the discovery of novel molecular insights. METHODS: In the current study, an optimized proteomics approach was employed to discover novel serum-based biomarkers for ESCC, and unveil abnormal signal pathways. Gene ontology (GO) enrichment analysis was done by Gene Set Enrichment Analysis (GSEA) and Metascape database, respectively. Pathway analysis was accomplished by GeneCards database. The correlation coefficient was assessed using Pearson and distance correlation analyses. Prioritized candidates were further verified in two independent validation sets by enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry (IHC) staining. RESULTS: A total of 633 non-redundant proteins were identified in the serum of patients with ESCC, of which 59 and 10 proteins displayed a more than 1.5-fold increase or decrease compared with healthy controls. Verification was performed for six candidate biomarkers, including S100A8/A9, SAA1, ENO1, TPI1 and PGAM1. Receiver operating characteristics (ROC) curve plotting showed the high diagnostic sensitivity and specificity of these six protein molecules as a biomarker panel: the area under characteristic curve (AUC) is up to 0.945. Differentially expressed proteins were subjected to functional enrichment analysis, which revealed the dysregulation of signaling pathways mainly involved in glycolysis, TLR4, HIF-1α, Cori cycle, TCA cycle, folate metabolism, and platelet degranulation. The latter finding was all the more noteworthy as a strong positive correlation was discovered between activated glycolysis and TLR4 pathways and unfavorable clinicopathological TNM stages in ESCC. CONCLUSIONS: Our findings propose a potential serum biomarker panel for the early detection and diagnosis of ESCC, which could potentially broaden insights into the characteristics of ESCC from the proteomic perspective.

Nrf3 Promotes 5-FU Resistance in Colorectal Cancer Cells via the NF-κB/BCL-2 Signaling Pathway In Vitro and In Vivo.

Increasing evidence indicates that nuclear factor, erythroid 2-like 3 (Nrf3) is connected with tumorigenesis. However, the relationship between Nrf3 and tumor drug resistance remains elusive. In this study, we investigated the effect and mechanism of action by which Nrf3 regulated the sensitivity of colon cancer cells to 5-fluorouracil (5-FU). We found Nrf3 was significantly increased in colon cancer tissues. Furthermore, we observed that Nrf3 knockdown and overexpression can significantly affect the sensitivity of colon cancer cells to 5-FU in vitro and in vivo. Moreover, Nrf3 promoted the expression of RELA, P-RELA, and BCL-2. Inhibition of NF-κB partly reversed the effects of Nrf3 overexpression, resulting in the resistance of colon cancer cells to 5-FU. Overall, the study revealed that Nrf3 was connected to the sensitivity of colon cancer cells to 5-FU, and its possible mechanism was related to the NF-κB signaling pathway, which provided a new target for overcoming the resistance of colon cancer cells to 5-FU.

12-Epi-Napelline Inhibits Leukemia Cell Proliferation via the PI3K/AKT Signaling Pathway In Vitro and In Vivo.

This study aimed to investigate the inhibitory effect of 12-epi-napelline on leukemia cells and its possible mechanisms. The inhibitory effects of 12-epi-napelline on K-562 and HL-60 cells were evaluated using the CCK-8 assay, cell cycle arrest and apoptosis were detected by flow cytometry, and the expression of related proteins was measured by western blot. A K-562 tumor model was established to evaluate the antitumor effect of 12-epi-napelline in vivo. A reduction in leukemia cell viability was observed after treatment with 12-epi-napelline. It was determined that the cell cycle was arrested in the G0/G1 phase, and the cell apoptosis rate was increased. Moreover, caspase-3 and Bcl-2 were downregulated, whereas cleaved caspase-3 and caspase-9 were upregulated. Further study revealed that 12-epi-napelline could suppress the expression of PI3K, AKT, p-AKT, and mTOR. Insulin-like growth factor 1 (IGF-1) attenuated 12-epi-napelline-induced apoptosis and ameliorated the repression of PI3K, AKT, p-AKT, and mTOR by 12-epi-napelline. Animal experiments clearly showed that 12-epi-napelline inhibited tumor growth. In conclusion, 12-epi-napelline restrained leukemia cell proliferation by suppressing the PI3K/AKT/mTOR pathway in vitro and in vivo.

The Effects and Mechanisms by which Saikosaponin-D Enhances the Sensitivity of Human Non-small Cell Lung Cancer Cells to Gefitinib.

Non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR)-sensitive mutations benefit from epidermal growth factor receptor tyrosine kinase inhibitors (EGFR- TKIs). However, drug resistance is a major cause of therapeutic failure. This study examined whether saikosaponin-d (SSD) enhances the anti-tumor effect of gefitinib in NSCLC cells. Cell Counting Kit-8 (CCK-8) was used to determine cell viability. Cell apoptosis was examined by flow cytometry. Signal transducer and activator of transcription (STAT3), phosphor-STAT3 (P-STAT3), and B-cell lymphoma 2 (Bcl-2) were detected by Western blot. An HCC827/GR tumor model was established to observe the effect of combination therapy in vivo. The combination of SSD with gefitinib had an enhanced inhibitory effect by reducing cell viability and inducing cells apoptosis in NSCLC cells. Furthermore, SSD decreased and increased the expression of P-STAT3 and Bcl-2, respectively. Down-regulated STAT3 promoted the sensitivity of lung cancer cells to gefitinib. The results of animal experiments also showed that SSD enhanced the anti-tumor effect of gefitinib. These results indicated that the combination of SSD with gefitinib had an increased antitumor effect in NSCLC cells and that the molecular mechanisms were associated with the inhibition of STAT3/Bcl-2 signaling pathway. Our findings suggest a promising approach for the treatment of NSCLC patients with EGFR-TKI resistance.

Pimozide suppresses colorectal cancer via inhibition of Wnt/ß-catenin signaling pathway.

OBJECTIVE: Wnt/ß­catenin signaling pathway plays important role in colorectal cancer (CRC) and acts as a potential therapeutic target. Pimozide is a FDA-approved clinical drug used to treat psychotic diseases and it has shown anticancer effect in some tumors partially via inhibition of Wnt/ß­catenin signaling pathway. This study aimed to investigate whether pimozide exerts anticancer effect on CRC and explore underlying mechanism. METHODS AND RESULTS: Pimozide was administrated to treat HCT116 and SW480 cells. Quantitative real-time polymerase chain reaction and western blot were used to detect the expression of epithelial-to-mesenchymal transition markers and Wnt/ß­catenin signaling pathway-related proteins. Cell proliferation and migration were measured by Cell Counting Kit-8 and Transwell assays respectively. HCT116 and SW480 cells were subcutaneously injected into nude mice and when the volume of tumor grown measureable (approximately 100 mm3) animals were treated with vehicle saline or pimozide at a dose of 25 mg/kg·d by oral gavage and then tumor size was measured at 7, 14, 21 and 28 days post treatment. Pimozide dose-dependently inhibited cell proliferation and migration in both HCT116 and SW480 cells, increased expression of E-cadherin and decreased expression of N­cadherin, vimentin and Snail. In addition, tumor growth was inhibited by pimozide in both HCT116 and SW480 xenografts in vivo. Expression of ß­catenin and Wnt target genes c-Myc, cyclin D1, Axin 2 and survivin was reduced by pimozide treatment in both HCT 116 and SW480 cells. CONCLUSION: Pimozide exerts anticancer effect in CRC via inhibition of wnt/ß­catenin signaling pathway, suggesting it as a potential therapeutic drug for CRC.

Shikonin enhances sensitization of gefitinib against wild-type EGFR non-small cell lung cancer via inhibition PKM2/stat3/cyclinD1 signal pathway.

AIMS: Mutant EGFR Non-small cell lung cancer has benefit from gefitinib, but it has limited effect for wild-type EGFR tumors. Shikonin, a natural naphthoquinone isolated from a traditional Chinese medicine, the plant Lithospermum erythrorhizon (zicao), not only can inhibit the tumor growth, but also overcome cancer drug resistance. Our aim is to investigate whether shikonin can enhance antitumor effect of gefitinib in EGFR wild-type lung cancer cells in vitro and in vivo. MATERIALS AND METHODS: CCK-8 was used to determine the proliferation of EGFR wild-type non-small cell lung cancer. Apoptosis and cell cycle were detected by flow cytometry. PKM2, STAT3, p-STAT3 and cyclinD1 were detected by Western blot. A549 tumor model was established to observe the antitumor effect of shikonin combination with gefitinib in vivo. KEY FINDINGS: The results showed that combination of shikonin with gefitinib exhibited synergistic antitumor effect in vitro and in vivo. Its potential molecular mechanisms may be associated with inhibition of PKM2/STAT3/cyclinD1. SIGNIFICANCE: These results provide a promising therapeutic approach for the treatment of wild-type EGFR non-small cell lung cancer.

Efficacy of Shikonin against Esophageal Cancer Cells and its possible mechanisms in vitro and in vivo.

Increasing evidences indicate that shikonin can suppress the tumor growth. However, the mechanisms remain elusive. In the present study, we investigated the effects and mechanisms of shikonin against esophageal cancer. The expression of hypoxia inducible factor 1α (HIF1α) and pyruvate kinase M2 (PKM2) in esophageal cancer tissues and cells was detected by immunohistochemistry and Western blot. CCK-8 was used to examine the esophageal cancer cell viability. Apoptosis and cell cycle were analyzed by flow cytometry. The expression of EGFR, PI3K, Akt, p-AKT, mTOR, HIF1α and PKM2 was detected by Western blot. EC109/pkm2 was established by lentivirus transducer. Ec109 tumor model was founded to observe the antitumor effect of shikonin in vivo. We found that HIF1α and PKM2 protein expression levels were higher in esophageal cancer tissues and cells than normal esophageal tissues and cells. Shikonin reduced esophageal cancer cells viability and induced cell cycle arrest and apoptosis. Shikonin decreased EGFR, PI3K, p-AKT, HIF1α and PKM2 expression. Overexpression of PKM2 could enhance resistance of esophageal cancer cells to shikonin. In vivo we found that shikonin reduced tumor burden, inducing cell arrest and apoptosis. Taken together, shikonin has a significant antitumor effect in the esophageal cancer by regulating HIF1α/PKM2 signal pathway.

Effects and Mechanisms of Metformin on the Proliferation of Esophageal Cancer Cells In Vitro and In Vivo.

PURPOSE: The purpose of this study was to observe the effects of metformin on human esophageal cancer cell and to investigate its possible mechanisms. MATERIALS AND METHODS: Cell viability was detected by using a Cell Counting Kit-8, while cell cycle and apoptosis were assessed by flow cytometry and western blot was used to measure the expression of the related proteins. RNAi was used to knockout pyruvate kinase muscle isozyme 2 (PKM2). An Eca109 tumor model was established to evaluate the antitumor effect in vivo. Immunohistochemistry was determined based on the expression of PKM2 and Bim in tumor tissues. Tunnel was used to assess tumor cell apoptosis. RESULTS: Esophageal cancer cells viability was reduced after metformin treatment. The cell cycle was arrested in the G0/G1 phase, apoptosis was induced, caspase 3 was activated, caspase 9 was downregulated, and the pro-apoptotic protein Bim increased. Further study revealed that metformin could suppress the expression of insulin-like growth factor 1 receptor and its downstream proteins, phosphoinositide 3-kinase (PI3K), protein kinase B (AKT/PKB), phosphorylation of AKT (pAKT), mammalian target of rapamycin (mTOR), p70S6K, and PKM2. Insulin-like growth factor 1 partly reversed metfromin-induced apoptosis and attenuated the repression effect of metfomin to PI3K, pAKT, and PKM2. Knockout PKM2 resulted in the activation of caspase 3, down-regulation of caspase 9, and increased expression of Bim. In the Eca109 xenograft model, metformin significantly reduced tumor growth. Furthermore, we found that metformin treatment increased the rate of apoptosis, down-regulation of PKM2, and up-regulation of Bim in tumor tissues. CONCLUSION: Metformin restrained esophageal cancer cell proliferation partly by suppressing the PI3K/AKT/mTOR pathway.

IL-7 inhibits tumor growth by promoting T cell-mediated antitumor immunity in Meth A model.

Immune suppression is well documented during tumor progression, which includes loss of effect of T cells and expansion of T regulatory (Treg) cells. IL-7 plays a key role in the proliferation, survival and homeostasis of T cells and displays a potent antitumor activity in vivo. In the present study, we investigated the antitumor effect of IL-7 in Meth A model. IL-7 inhibited tumor growth and prolonged the survival of tumor-bearing mice with corresponding increases in the frequency of CD4 and CD8 T cells, Th1 (CD4(+)IFN-γ(+)), Tc1 (CD8(+)IFN-γ(+)) and T cells cytolytic activity against Meth A cells. Neutralization of CD4 or CD8 T cells reversed the antitumor benefit of IL-7. Furthermore, IL-7 decreased regulatory T Foxp3 as well as cells suppressive activity with a reciprocal increase in SMAD7. In addition, we observed an increase of the serum concentrations of IL-6 and IFN-γ, and a significant decrease of TGF-ß and IL-10 after IL-7 treatment. Taken together, these results indicate that IL-7 augments T cell-mediated antitumor immunity and improves the effect of antitumor in Meth A model.

Enhanced antitumor effect of curcumin liposomes with local hyperthermia in the LL/2 model.

Curcumin previously was proven to inhibit angiogenesis and display potent antitumor activity in vivo and in vitro. In the present study, we investigated whether a combination curcumin with hyperthermia would have a synergistic antitumor effect in the LL/2 model. The results indicated that combination therapy significantly inhibited cell proliferation of MS-1 and LL/2 in vitro. LL/2 experiment model also demonstrated that the combination therapy inhibited tumor growth and prolonged the life span in vivo. Furthermore, combination therapy reduced angiogenesis and increased tumor apoptosis. Our findings suggest that the combination therapy exerted synergistic antitumor effects, providing a new perspective fpr clinical tumor therapy.