Dataset Information

Inhibiting the NF-?B pathway enhances the antitumor effect of cabazitaxel by downregulating Bcl-2 in pancreatic cancer.

ABSTRACT: Optimizing the currently available treatment options for pancreatic cancer (PC) is a priority. Cabazitaxel (CTX), a semisynthetic taxane, is mainly used for treating patients with PC who are resistant to paclitaxel (PTX) or docetaxel, due its poor affinity for P?glycoprotein. However, there are only a few studies demonstrating the effect of CTX on PC. The present study aimed to investigate the efficiency and underlying mechanism of CTX in PC treatment. Cell proliferation, colony formation assay and apoptosis analysis were achieved in the two human PC cell lines AsPC?1 and BxPC?3. Drug sensitivity test was performed in BxPC?3 tumor?bearing mice. The results demonstrated that CTX had a lower half maximal inhibitory concentration compared with PTX for the inhibition of cell proliferation, both in vivo and in vitro. Furthermore, the nuclear factor??B (NF??B) pathway was activated following cell treatment with CTX, and NF??B p65 overexpression attenuated CTX cytotoxicity. In addition, the combined use of the specific NF??B inhibitor caffeic acid phenethyl ester (CAPE) with CTX significantly enhanced CTX effect, both in vivo and in vitro. Similarly, the mRNA and protein expression of B?cell lymphoma-2 was decreased in AsPC?1 and BxPC?3 cells following treatment with CTX and CAPE, suggesting that NF??B may serve a crucial role in CTX efficiency. In conclusion, results from our previous study indicated that CTX could potentially replace PTX in the treatment of PC, and the present study demonstrated that CTX combination with an NF??B inhibitor may be considered as a potential therapeutic option for PC, which may improve the prognosis of patients with PC.

SUBMITTER: Li Z

PROVIDER: S-EPMC7252454 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Inhibiting the NF-κB pathway enhances the antitumor effect of cabazitaxel by downregulating Bcl-2 in pancreatic cancer.

Li Zequn Z Xuan Zefeng Z Chen Jian J Song Wenfeng W Zhang Shiyu S Jin Cheng C Zhou Mengqiao M Zheng Shusen S Song Penghong P

International journal of oncology 20200427 1

Optimizing the currently available treatment options for pancreatic cancer (PC) is a priority. Cabazitaxel (CTX), a semisynthetic taxane, is mainly used for treating patients with PC who are resistant to paclitaxel (PTX) or docetaxel, due its poor affinity for P‑glycoprotein. However, there are only a few studies demonstrating the effect of CTX on PC. The present study aimed to investigate the efficiency and underlying mechanism of CTX in PC treatment. Cell proliferation, colony formation assay ...[more]

PMID: 32377719

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Project description:Glioblastoma (GBM) is one of the most lethal primary brain tumor with a poor median survival less than 15 months. Despite the development of the clinical strategies over the decades, the outcomes for GBM patients remain dismal due to the strong proliferation and invasion ability and the acquired resistance to radiotherapy and chemotherapy. Therefore, developing new biomarkers and therapeutic strategies targeting GBM is in urgent need. In this study, gene expression datasets and relevant clinical information were extracted from public cancers/glioma datasets, including TCGA, GRAVENDEEL, REMBRANDT, and GILL datasets. Differentially expressed genes were analyzed and NEK2 was picked as a candidate gene for subsequent validation. Human tissue samples and corresponding data were collected from our center and detected by immunohistochemistry analysis. Molecular biological assays and in vivo xenograft transplantation were performed to confirm the bioinformatic findings. High-throughput RNA sequencing, followed by KEGG analysis, GSEA analysis and GO analysis were conducted to identify potential signaling pathways related to NEK2 expression. Subsequent mechanism assays were used to verify the relationship between NEK2 and NF-κB signaling. Overall, we identified that NEK2 is significantly upregulated in GBM and the higher expression of NEK2 exhibited a poorer prognosis. Functionally, NEK2 knockdown attenuated cell proliferation, migration, invasion, and tumorigenesis of GBM while NEK2 overexpression promoted the GBM progression. Furthermore, High-throughput RNA sequencing and bioinformatics analysis indicated that NEK2 was positively related to the NF-κB signaling pathway in GBM. Mechanically, NEK2 activated the noncanonical NF-κB signaling pathway by phosphorylating NIK and increasing the activity and stability of NIK. In conclusion, NEK2 promoted the progression of GBM through activation of noncanonical NF-κB signaling, indicating that NEK2- NF-κB axis could be a potential drug target for GBM.

Dataset Information

Inhibiting the NF-?B pathway enhances the antitumor effect of cabazitaxel by downregulating Bcl-2 in pancreatic cancer.

Publications

Inhibiting the NF-κB pathway enhances the antitumor effect of cabazitaxel by downregulating Bcl-2 in pancreatic cancer.

Similar Datasets

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