B7-H3 Silencing Increases Paclitaxel Sensitivity by Abrogating Jak2/Stat3 Phosphorylation

Liu, Hao; Tekle, Christina; Chen, Yih Wen; Kristian, Alexander; Zhao, Yuhua; Zhou, Ming; Liu, Zixing; Ding, Yan; Wang, Bin; Mælandsmo, Gunhild Mari; Nesland, Jahn M.; Fodstad, Øystein; Tan, Ming

doi:10.1158/1535-7163.mct-11-0072

Cited by 130 publications

(125 citation statements)

References 41 publications

Supporting

Mentioning

115

Contrasting

Unclassified

Order By: Relevance

“…The growth of established B7-H3 knockdown Maver and Z138 xenografts slowed down compared with their NC groups by 59.1 and 65.0% at the end of observation, respectively. The similar growth inhibition of B7-H3-knockdown xenografts in glioma (22), breast cancer (26) and pancreatic cancer (23) has been observed in other reseach. Furthermore, we found that the expressions of Ki-67 and PCNA were significantly decreased in the B7-H3 silenced MCL xenografts.…”

Section: Discussionsupporting

confidence: 81%

“…The synergistic cell apoptotic effects in Maver and Z138 cells induced by R and Ben were promoted by B7-H3 knockdown in a time-dependent manner. It indicates that B7-H3 knockdown enhances drug-induced cytotoxicity and apoptosis, and a similar conclusion was drawn in B7-H3 silenced breast cancer cells treated with paclitaxel (26). Furthermore, we detected the activity of caspase-3 in Maver and Z138 cells incubated with R and/or Ben for 24 h, which is the mitochondrial downstream effector caspase in apoptosis signaling cascades.…”

Section: Discussionsupporting

confidence: 78%

“…Other studies also reported that B7-H3 was important in regulating the adhesive, migratory, and invasive capacity in breast cancer (21), glioblastoma (22), pancreatic cancer (23), prostate cancer (24) and osteosarcoma (25). Liu et al discovered that silencing of B7-H3 sensitized the breast cancer cell lines to paclitaxel by abrogating Jak2/Stat3 phosphorylation (26). In pancreatic carcinoma cells, B7-H3 was demonstrated to induce gemcitabine resistance as well (27).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

B7-H3 silencing inhibits tumor progression of mantle cell lymphoma and enhances chemosensitivity

Zhang

Wang

et al. 2015

International Journal of Oncology

View full text Add to dashboard Cite

Abstract. B7-H3 (CD276), known as a member of B7 immunoregulatory family, is a type I transmembrane glycoprotein aberrantly expressed in numerous types of cancer and associated with poor prognosis. However, the role of B7-H3 in oncogenesis and chemosensitivity of mantle cell lymphoma (MCL) remains unknown. We determined the effects of downregulating B7-H3 expression on tumor progression and the sensitivity of chemotherapeutic drug in mantle cell lymphoma. B7-H3 knockdown was performed using lentivirus transduction in the Maver and Z138 mantle cell lymphoma cell lines, respectively. The effects of B7-H3 on cell proliferation, cycle, migration and invasion were investigated by CCK-8 assay, methyl cellulose colony forming assay, PI staining, and Transwell assays in vitro. By establishing Maver and Z138 xenograft models, the effects of B7-H3 on tumorigenicity were observed, and Ki-67 and PCNA was detected by immunohistochemistry. The downregulation of B7-H3 significantly decreased tumor proliferation in MCL in vitro and in vivo. In the B7-H3 knockdown groups of Maver and Z138 xenograft models, the mean inhibition rate of tumor growth was 59.1 and 65.0% (p=0.010 and 0.003), and the expression of both Ki-67 and PCNA were significantly lower, respectively. After B7-H3 silencing, the cell cycles of Maver and Z138 were both arrested at G0/G1 phase, and the cell migration rates and invasion capacity were decreased as well. Moreover, the impacts of B7-H3 RNAi on the antitumor effect of chemotherapy drugs were determined with CCK-8 and Annexin V-FITC/PI assays in vitro and with xenograft models in vivo. The silencing of B7-H3 increased the sensitivity of Maver and Z138 cells to rituximab and bendamustine and enhanced the drug-induced apoptosis, respectively. Our study demonstrates for the first time that B7-H3 promotes mantle cell lymphoma progression and B7-H3 knockdown significantly enhances the chemosensitivity. This may provide a new therapeutic approach to mantle cell lymphoma. IntroductionMantle cell lymphoma (MCL), a heterogeneous subtype of B-cell non-Hodgkin lymphoma (NHL), accounts for ~7% of NHL cases in the USA and Europe and has one of the worst outcomes of all the lymphomas (1,2). It is characterized by the t(11;14) (q13;q32) translocation, which results in overexpression of cyclin D1 and deregulation of the cell cycle (2). At initial diagnosis, most patients with the median age ~68-70 years have advanced stage disease, and the median overall survival is 3-5 years (3). Although several novel agents have proven to be effective, MCL remains a largely incurable disease and the following relapse is still challenging. Therefore, understanding the molecular mechanisms of MCL pathogenesis and drug resistance will aid in the development of highly active targeted therapies for the disease.B7-H3, a new member of B7 immunoregulatory family with immunoglobulin-like structure (4), is induced in activated dendritic cells, monocytes and T cells (5). Aberrant expression of B7-H3 has been reported and associated with poor prog...

show abstract

Section: Discussionsupporting

confidence: 81%

Section: Discussionsupporting

confidence: 78%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

B7-H3 silencing inhibits tumor progression of mantle cell lymphoma and enhances chemosensitivity

Zhang

Wang

et al. 2015

International Journal of Oncology

View full text Add to dashboard Cite

show abstract

“…The JAK2/STAT3 signaling pathway is commonly associated with the emergence of apoptosis resistance in cancer cells, thus representing a potential target for anticancer therapy (26,27). The data in the current study revealed that MUC1 overexpression significantly enhanced the phosphorylation of JAK2 and STAT3 in irradiated HCC cells.…”

Section: Discussionsupporting

confidence: 50%

Mucin 1 promotes radioresistance in hepatocellular carcinoma cells through activation of JAK2/STAT3 signaling

2017

Oncol Lett

View full text Add to dashboard Cite

Abstract. Mucin 1 (MUC1) is aberrantly overexpressed in numerous human cancer types, including hepatocellular carcinoma (HCC) and contributes to chemoresistance of tumor cells. The aim of the present study was to evaluate the possible implication of MUC1 in radioresistance of HCC cells and the underlying mechanisms. It was demonstrated that MUC1 was significantly upregulated in HCC cells following irradiation exposure, which was coupled with increased phosphorylation of signal transducer and activator of transcription 3 (STAT3). Enforced expression of MUC1 significantly (P<0.05) promoted the clonogenic survival of HCC cells following irradiation compared with empty vector-transfected cells. MUC1 overexpression resulted in >60% reduction in apoptosis induced by irradiation, as determined by Annexin-V/propidium iodide double staining and flow cytometry analysis. Furthermore, overexpression of MUC1 significantly (P<0.05) attenuated the activation of caspase-3 and poly (ADP-ribose) polymerase in response to irradiation exposure. Mechanistically, MUC1 inhibited irradiation-induced apoptosis through activation of janus kinase 2 (JAK2) and STAT3, and induction of anti-apoptotic proteins induced myeloid leukemia cell differentiation protein Mcl-1 (Mcl-1) and BCL2 like 1 (Bcl-xL). Small hairpin RNA-mediated knockdown of STAT3 or MUC1 resensitized MUC1-overexpressing cells to irradiation-induced apoptosis, which was accompanied by reduced expression of Bcl-xL and Mcl-1. Collectively, MUC1 contributes to radioresistance of HCC cells likely through activation of the JAK2/STAT3 signaling pathway and thus represents a potential target for improving radiotherapy against HCC.

show abstract

“…We supposed that this type of molecules may be more closely related to resistance to a specific type of drug but not to the multidrug resistance. Secondly, because of the complexity of non-glycopeptide sample and the undersampling of MS, glycoproteins, such as B7-H3 which was reported to be associated with resistance to paclitaxel in breast cancer cells, can be identified with glycopeptides, but the non-glycopeptide information of them cannot be collected [41]. Therefore we did not subject them for further analysis, either.…”

Section: Discussionmentioning

confidence: 99%

In-depth research of multidrug resistance related cell surface glycoproteome in gastric cancer

Li¹,

Sun²,

Zheng³

et al. 2013

Journal of Proteomics

View full text Add to dashboard Cite

B7-H3 Silencing Increases Paclitaxel Sensitivity by Abrogating Jak2/Stat3 Phosphorylation

Cited by 130 publications

References 41 publications

B7-H3 silencing inhibits tumor progression of mantle cell lymphoma and enhances chemosensitivity

B7-H3 silencing inhibits tumor progression of mantle cell lymphoma and enhances chemosensitivity

Mucin 1 promotes radioresistance in hepatocellular carcinoma cells through activation of JAK2/STAT3 signaling

In-depth research of multidrug resistance related cell surface glycoproteome in gastric cancer

Contact Info

Product

Resources

About