scholarly journals Thymosin β10 promotes tumor-associated macrophages M2 conversion and proliferation via the PI3K/Akt pathway in lung adenocarcinoma

2020 ◽  
Author(s):  
Jun Zeng ◽  
Li Yang ◽  
Yaxin Zheng
Keyword(s):  
Lung Adenocarcinoma ◽  
Progression Free Survival ◽  
Tumor Biomarker ◽  
Mice Model ◽  
Thymosin Β10 ◽  
Xenograft Mice Model ◽  
Raw264.7 Cell ◽  
Lung Adenocarcinomas

Abstract Background: Thymosin β10 (TMSB10) has been reported to play a protumorigenic role in a majority of solid cancers. However, the function of TMSB10 in immune microenvironment may contribute to the pathobiology of lung adenocarcinoma has not been previously explored.Method: TAMs-associated TMSB10 expression was evaluated by immunohistochemistry (IHC) of 184 lung adenocarcinomas. Xenograft mice model was established to investigate the effect of TMSB10 shRNA on TAMs. The macrophages phenotype associated cytokines IL-6, IL-8 and TNF-α were detected by ELISA. Furthermore, the target proteins were detected by immunoblot.Results: We found that high TAMs-associated TMSB10 expression was significantly correlated with the advanced TNM stage and T3/T4 tumor size. And high TAMs-associated TMSB10 expression was significantly correlated with poor overall and progression-free survival of lung adenocarcinoma, acted as an independent prognostic factor for lung adenocarcinoma. Furthermore, we investigated the biological functions of TMSB10 in macrophages in vivo and in vitro. TMSB10 knockdown dramatically reduced TAMs, THP-1 and RAW264.7 cell proliferation, and promoted macrophages conversion of M2 to M1, and TMSB10 knockdown reduced the levels of p-Akt (Sec473), p-mTOR (Sec2448) and p-p70S6K (Thr389) without effect on Akt, mTOR and p70S6K expression.Conclusions: These results demonstrate that TAMs-associated TMSB10 promotes tumor growth through increasing TAMs M2 conversion and proliferation via PI3K/Akt signaling pathway, providing a promising tumor biomarker for predicting prognosis and a potential therapeutic target for lung adenocarcinoma.

scholarly journals Thymosin β10 promotes tumor-associated macrophages M2 conversion and proliferation via the PI3K/Akt pathway in lung adenocarcinoma

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Jun Zeng ◽  
Xianggui Yang ◽  
Li Yang ◽  
Wancheng Li ◽  
Yaxin Zheng
Keyword(s):  
Lung Adenocarcinoma ◽  
Progression Free Survival ◽  
Tumor Biomarker ◽  
Mice Model ◽  
Thymosin Β10 ◽  
Xenograft Mice Model ◽  
Raw264.7 Cell ◽  
Lung Adenocarcinomas

Abstract Background Thymosin β10 (TMSB10) has been reported to play a protumorigenic role in a majority of solid cancers. However, the existence of TMSB10 in immune microenvironment may contribute to the pathogenesis of lung adenocarcinoma has not been previously explored. Method TAMs-associated TMSB10 expression was evaluated by immunohistochemistry (IHC) in 184 lung adenocarcinomas. Xenograft mice model was established to investigate the effect of TMSB10 shRNA on TAMs phenotypes. The macrophages phenotype associated cytokines IL-6, IL-8, IL-12 and TNF-α were detected by ELISA after treated with TMSB10 shRNA or scramble. Furthermore, the target proteins were detected by immunoblotting. Results We found that high TAMs-associated TMSB10 expression was significantly correlated with the advanced TNM stage and T3/T4 tumor size. And high TAMs-associated TMSB10 expression was significantly correlated with poor overall and progression-free survival of lung adenocarcinoma, acting as an independent prognostic factor for lung adenocarcinoma. Furthermore, we investigated the biological functions of TMSB10 in macrophages in vivo and in vitro. TMSB10 knockdown dramatically reduced TAMs, THP-1 and RAW264.7 cell proliferation, and promoted macrophages phenotype conversion of M2 to M1, and TMSB10 knockdown reduced the levels of p-Akt (Sec473), p-mTOR (Sec2448) and p-p70S6K (Thr389) without effect on Akt, mTOR and p70S6K expression. Conclusions These results demonstrate that TAMs-associated TMSB10 promotes tumor growth through increasing TAMs M2 conversion and proliferation via PI3K/Akt signaling pathway, providing a promising tumor biomarker for predicting prognosis and a potential therapeutic target for lung adenocarcinoma.

scholarly journals Thymosin β10 promotes tumor-associated macrophages M2 conversion and proliferation via the PI3K/Akt pathway in lung adenocarcinoma

2020 ◽  
Author(s):  
Jun Zeng ◽  
Xianggui Yang ◽  
Li Yang ◽  
Wancheng Li ◽  
Yaxin Zheng
Keyword(s):  
Lung Adenocarcinoma ◽  
Progression Free Survival ◽  
Tumor Biomarker ◽  
Mice Model ◽  
Thymosin Β10 ◽  
Xenograft Mice Model ◽  
Raw264.7 Cell ◽  
Lung Adenocarcinomas

Abstract Background: Thymosin β10 (TMSB10) has been reported to play a protumorigenic role in a majority of solid cancers. However, the existence of TMSB10 in immune microenvironment may contribute to the pathogenesis of lung adenocarcinoma has not been previously explored. Method: TAMs-associated TMSB10 expression was evaluated by immunohistochemistry (IHC) in 184 lung adenocarcinomas. Xenograft mice model was established to investigate the effect of TMSB10 shRNA on TAMs phenotypes. The macrophages phenotype associated cytokines IL-6, IL-8, IL-12 and TNF-α were detected by ELISA after treated with TMSB10 shRNA or scramble. Furthermore, the target proteins were detected by immunoblot. Results: We found that high TAMs-associated TMSB10 expression was significantly correlated with the advanced TNM stage and T3/T4 tumor size. And high TAMs-associated TMSB10 expression was significantly correlated with poor overall and progression-free survival of lung adenocarcinoma, acting as an independent prognostic factor for lung adenocarcinoma. Furthermore, we investigated the biological functions of TMSB10 in macrophages in vivo and in vitro. TMSB10 knockdown dramatically reduced TAMs, THP-1 and RAW264.7 cell proliferation, and promoted macrophages phenotype conversion of M2 to M1, and TMSB10 knockdown reduced the levels of p-Akt (Sec473), p-mTOR (Sec2448) and p-p70S6K (Thr389) without effect on Akt, mTOR and p70S6K expression. Conclusions: These results demonstrate that TAMs-associated TMSB10 promotes tumor growth through increasing TAMs M2 conversion and proliferation via PI3K/Akt signaling pathway, providing a promising tumor biomarker for predicting prognosis and a potential therapeutic target for lung adenocarcinoma.

scholarly journals Co-Treatment with the Epigenetic Drug, 3-Deazaneplanocin A (DZNep) and Cisplatin after DZNep Priming Enhances the Response to Platinum-Based Therapy in Chondrosarcomas

Cancers ◽  
2021 ◽  
Vol 13 (18) ◽  
pp. 4648
Author(s):  
Eva Lhuissier ◽  
Juliette Aury-Landas ◽  
Marion Lenté ◽  
Karim Boumediene ◽  
Catherine Baugé
Keyword(s):  
Tumor Volume ◽  
Mice Model ◽  
Antitumoral Effect ◽  
Viable Cells ◽  
Epigenetic Drug ◽  
Xenograft Mice Model ◽  
Xenograft Mice ◽  
Tumoral Cells

Background: We have previously shown that 3-Deazaneplanocin A (DZNep) induces apoptosis in chondrosarcomas. Herein, we tested whether the combination of this epigenetic drug to a standard anticancer therapy may enhance the response to each drug in these bone tumors. Methods: Two chondrosarcoma cell lines (SW1353 and JJ012) were cultured in the presence of DZNep and/or cisplatin. Cell growth was evaluated by counting viable cells, and apoptosis was determined by Apo2.7 expression by flow cytometry. In vivo, the antitumoral effect of the DZNep/cisplatin combination was assessed through measurements of tumor volume of JJ012 xenografts in nude mice. Results: In vitro, the DZNep/cisplatin combination reduced cell survival and increased apoptosis compared to each drug alone in chondrosarcomas, but not in normal cells (chondrocytes). This enhancement of the antitumoral effect of the DZNep/cisplatin combination required a priming incubation with DZNep before the co-treatment with DZNep/cisplatin. Furthermore, in the chondrosarcoma xenograft mice model, the combination of both drugs more strongly reduced tumor growth and induced more apoptosis in tumoral cells than each of the drugs alone. Conclusion: Our results show that DZNep exposure can presensitize chondrosarcoma cells to a standard anticancer drug, emphasizing the promising clinical utilities of epigenetic-chemotherapeutic drug combinations in the future treatment of chondrosarcomas.

scholarly journals Knockdown of 91 H Suppresses the Tumorigenesis of Osteosarcoma via Inducing Methylation of CDK4 Promoter

2021 ◽  
Vol 20 ◽  
pp. 153303382199000
Author(s):  
Suoli Cheng ◽  
Jianping Zheng ◽  
Xueqin Liu ◽  
Jiandang Shi ◽  
Fan Gong ◽  
...  
Keyword(s):  
Cell Apoptosis ◽  
Migration And Invasion ◽  
G1 Arrest ◽  
Osteosarcoma Cells ◽  
Mice Model ◽  
Primary Malignancy ◽  
Specific Pcr ◽  
Xenograft Mice Model

Background: Osteosarcoma is the most leading primary malignancy of the bone in adolescents all over the world. Long non-coding RNA (lncRNA) 91 H has been reported to participated in multiple cancers. Meanwhile, lncRNA 91 H has been proved to be upregulated in osteosarcoma. However, the function of 91 H in osteosarcoma remains unclear. Methods: Gene and protein expressions in osteosarcoma cells were detected by qRT-PCR and western blot, respectively. Cell viability was tested by CCK-8 assay. Ki67 staining was used to measure cell proliferation. Cell apoptosis and cycle were assessed by flow cytometry. In addition, transwell assay was used to detect cell migration and invasion. Furthermore, Methylation-specific PCR (MSP) was performed to test the methylation of CDK4 promoter. Finally, xenograft mice model was established to explore the role of 91 H in osteosarcoma in vivo. Results: Knockdown of 91 H significantly inhibited the growth of osteosarcoma cells via inducing the cell apoptosis. In addition, 91 H siRNA notably suppressed the migration and invasion of osteosarcoma cells. Meanwhile, knockdown of 91 H inhibited the progression of osteosarcoma via inducing methylation of CDK4 promoter. Furthermore, 91 H knockdown obviously induced G1 arrest in osteosarcoma cells via inhibition of PCNA and Cyclin D1. Finally, knockdown of 91 H notably inhibited the tumor growth of osteosarcoma in vivo. Conclusion: knockdown of 91 H suppressed the tumorigenesis of osteosarcoma via inducing methylation of CDK4 promoter in vitro and in vivo. Thus, 91 H may serve as a new target for the treatment of osteosarcoma.

scholarly journals The Deubiquitinating Enzyme Inhibitor PR-619 Enhances the Cytotoxicity of Cisplatin via the Suppression of Anti-Apoptotic Bcl-2 Protein: In Vitro and In Vivo Study

Cells ◽  
2019 ◽  
Vol 8 (10) ◽  
pp. 1268 ◽  
Author(s):  
Kuan-Lin Kuo ◽  
Shing-Hwa Liu ◽  
Wei-Chou Lin ◽  
Po-Ming Chow ◽  
Yu-Wei Chang ◽  
...  
Keyword(s):  
Antitumor Effect ◽  
Enzyme Inhibitor ◽  
Critical Role ◽  
Deubiquitinating Enzymes ◽  
Mice Model ◽  
Bladder Urothelial Carcinoma ◽  
Xenograft Mice Model ◽  
Xenograft Mice

After chemotherapy for the treatment of metastatic bladder urothelial carcinoma (UC), most patients inevitably encounter drug resistance and resultant treatment failure. Deubiquitinating enzymes (DUBs) remove ubiquitin from target proteins and play a critical role in maintaining protein homeostasis. This study investigated the antitumor effect of PR-619, a DUBs inhibitor, in combination with cisplatin, for bladder UC treatment. Our results showed that PR-619 effectively induced dose- and time-dependent cytotoxicity, apoptosis, and ER-stress related apoptosis in human UC (T24 and BFTC-905) cells. Additionally, co-treatment of PR-619 with cisplatin potentiated cisplatin-induced cytotoxicity in UC cells and was accompanied by the concurrent suppression of Bcl-2. We also proved that Bcl-2 overexpression is related to the chemo-resistant status in patients with metastatic UC by immunohistochemistry (IHC) staining. In a xenograft mice model, we confirmed that PR-619 enhanced the antitumor effect of cisplatin on cisplatin-naïve and cisplatin-resistant UCs. Our results demonstrated that PR-619 effectively enhanced the cisplatin-induced antitumor effect via concurrent suppression of the Bcl-2 level. These findings provide promising insight for developing a therapeutic strategy for UC treatment.

Synthetic investigation on chirally pure Mannich derivatives of pseudophenylpropanolamine and their anticancer properties against HepG-2 cells with inhibition of JAK2/STAT3

RSC Advances ◽  
2016 ◽  
Vol 6 (99) ◽  
pp. 96946-96962 ◽  
Author(s):  
C. Balachandran ◽  
K. Chennakesava Rao ◽  
Y. Arun ◽  
N. Emi ◽  
N. Yamamoto ◽  
...  
Keyword(s):  
Mice Model ◽  
Anticancer Properties ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway ◽  
Xenograft Mice Model ◽  
Xenograft Mice ◽  
Derivatives Of ◽  
Synthetic Investigation

In vitro and in vivo anticancer activity of compound 3a was proved as a novel blocker of JAK2/STAT3 signaling pathway and exerts both anti-proliferative and apoptotic activities in HepG-2 cells with xenograft mice model.

scholarly journals Hsa_circ_0020850 promotes the malignant behaviors of lung adenocarcinoma by regulating miR-326/BECN1 axis

2022 ◽  
Vol 20 (1) ◽  
Author(s):  
Xiaoju Li ◽  
Shengtian Su ◽  
Dan Ye ◽  
Zhigao Yu ◽  
Wenjing Lu ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Quantitative Polymerase Chain Reaction ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Circular Rnas ◽  
Mice Model ◽  
Adenocarcinoma Cells ◽  
Lung Adenocarcinoma Cells

Abstract Background Circular RNAs (circRNAs) are a novel type of endogenous RNAs and play vital roles in lung adenocarcinoma. However, the function and underlying mechanism of circ_0020850 in lung adenocarcinoma remain unknown. Methods The levels of circ_0020850, microRNA-326 (miR-326), and Beclin1 (BECN1) were analyzed by real-time quantitative polymerase chain reaction and western blot analyses. The migration and invasion were determined by wound healing and transwell assays, respectively. Colony formation assay was used to assess cell proliferation ability. The angiogenic ability was analyzed by Matrigel angiogenesis assay. The apoptosis rate was calculated by flow cytometry assay. Dual-luciferase reporter, RNA immunoprecipitation (RIP), and RNA pull-down assays were conducted to confirm the interaction relationship among circ_0020850, miR-326, and BECN1. A xenograft mice model was established to assess the role of circ_0020850 in vivo. Results We found that circ_0020850 was obviously overexpressed in lung adenocarcinoma tissues and cells. Knockdown of circ_0020850 inhibited migration, invasion, proliferation, and angiogenesis but induced apoptosis in lung adenocarcinoma cells in vitro, as well as curbed tumor growth in vivo. MiR-326 was a target of circ_0020850, and knockdown of miR-326 abolished the suppression effect of circ_0020850 on the malignant behaviors of lung adenocarcinoma cells. Additionally, miR-326 could negatively regulate BECN1 expression, thereby regulating lung adenocarcinoma cell phenotypes. Importantly, circ_0020850 could directly bind to miR-326 and thus relieve miR-326-mediated inhibition on BECN1. Conclusion Circ_0020850 promoted the malignant development of lung adenocarcinoma by regulating miR-326/BECN1 axis, indicating that circ_0020850 might serve as a promising target for the diagnosis and treatment of lung adenocarcinoma patients.

scholarly journals Combined Treatment with Doxorubicin and Rapamycin Is Effective against In Vitro and In Vivo Models of Human Glioblastoma

2019 ◽  
Vol 8 (3) ◽  
pp. 331 ◽  
Author(s):  
Anna Iorio ◽  
Martina Da Ros ◽  
Claudio Pisano ◽  
Maurizio de Martino ◽  
Lorenzo Genitori ◽  
...  
Keyword(s):  
Prolonged Exposure ◽  
Combined Treatment ◽  
Poor Responder ◽  
Tumor Growth Inhibition ◽  
Mice Model ◽  
In Vivo Models ◽  
Pharmacological Approach ◽  
Xenograft Mice Model

Despite numerous clinical trials, glioblastoma (GBM) remains a tumor that is difficult to treat. The aim of this study was to investigate the potential of a new pharmacological approach, combining doxorubicin (Dox) and rapamycin (Rapa), in in vitro and in vivo GBM models. Cytotoxic and anti-proliferative effects of Rapa plus Dox treatments were analyzed in GBM cell lines. The in vivo effectiveness of these treatments was investigated in an orthotopic xenograft mice model of GBM. In vitro results demonstrated that prolonged exposure to Rapa sensitize GBM cells to Dox treatments. In vivo results demonstrated that Rapa (5 mg/kg) plus Dox (5 mg/kg) determined the major tumor growth inhibition (−97.29% vs. control) but results in greater toxicity. The combination Rapa plus Dox (2.5 mg/kg) showed a tumor inhibition like Rapa plus Dox (5 mg/kg) with a toxicity comparable to Rapa alone. Thus, this study demonstrated the efficacy of this pharmacological approach, providing the rationale for a clinical application of this combinational therapy in “poor-responder” GBM patients.

scholarly journals Biejiajian Pill Inhibits Carcinogenesis and Metastasis via the Akt/GSK-3β/Snail Signaling Pathway in Hepatocellular Carcinoma

2021 ◽  
Vol 12 ◽  
Author(s):  
Jialing Sun ◽  
Weicong Chen ◽  
Bin Wen ◽  
Mingjia Zhang ◽  
Haitao Sun ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Molecular Mechanisms ◽  
Epithelial Mesenchymal Transition ◽  
Mice Model ◽  
Mesenchymal Transition ◽  
Signaling Axis ◽  
Xenograft Mice Model ◽  
Gsk 3Β

Hepatocellular carcinoma (HCC) is among the most usual cancers globally. In China, Biejiajian pill (BJJP), Traditional Chinese Medicine clinical prescription, is broadly utilized for the prevention and therapy of HCC. However, the mechanisms by which BJJP exerts its effects on the prevention of tumor invasion and metastasis are still largely unknown. In this study, in vitro multiple hepatic cancer cell lines and an in vivo xenograft mice model were used to validate the preventive effects and molecular mechanisms of BJJP in HCC. We established that BJJP significantly repressed the proliferation, metastasis and infiltration of HCC cells. Furthermore, BJJP remarkably suppressed HCC cell migration, as well as invasion via epithelial-mesenchymal transition (EMT) by modulating Snail expression, which was associated with the repression of Akt/GSK-3β/Snail signaling axis activation. In vivo HCC xenograft results indicated that BJJP delayed HCC development and efficiently inhibited lung metastasis. Taken together, BJJP was shown to be an effective therapeutic agent against HCC through repression of the Akt/GSK-3β/Snail signaling cascade and EMT.

Sign in / Sign up

Export Citation Format

Share Document