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

  • Authors:
    • Zequn Li
    • Zefeng Xuan
    • Jian Chen
    • Wenfeng Song
    • Shiyu Zhang
    • Cheng Jin
    • Mengqiao Zhou
    • Shusen Zheng
    • Penghong Song
  • View Affiliations / Copyright

    Affiliations: Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang, Hangzhou 310003, P.R. China
    Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 161-170
    |
    Published online on: April 27, 2020
       https://doi.org/10.3892/ijo.2020.5053
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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‑κB (NF‑κB) pathway was activated following cell treatment with CTX, and NF‑κB p65 overexpression attenuated CTX cytotoxicity. In addition, the combined use of the specific NF‑κB 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‑κB 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‑κB inhibitor may be considered as a potential therapeutic option for PC, which may improve the prognosis of patients with PC.
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Copy and paste a formatted citation
Spandidos Publications style
Li Z, Xuan Z, Chen J, Song W, Zhang S, Jin C, Zhou M, Zheng S and Song P: Inhibiting the NF-κB pathway enhances the antitumor effect of cabazitaxel by downregulating Bcl-2 in pancreatic cancer. Int J Oncol 57: 161-170, 2020.
APA
Li, Z., Xuan, Z., Chen, J., Song, W., Zhang, S., Jin, C. ... Song, P. (2020). Inhibiting the NF-κB pathway enhances the antitumor effect of cabazitaxel by downregulating Bcl-2 in pancreatic cancer. International Journal of Oncology, 57, 161-170. https://doi.org/10.3892/ijo.2020.5053
MLA
Li, Z., Xuan, Z., Chen, J., Song, W., Zhang, S., Jin, C., Zhou, M., Zheng, S., Song, P."Inhibiting the NF-κB pathway enhances the antitumor effect of cabazitaxel by downregulating Bcl-2 in pancreatic cancer". International Journal of Oncology 57.1 (2020): 161-170.
Chicago
Li, Z., Xuan, Z., Chen, J., Song, W., Zhang, S., Jin, C., Zhou, M., Zheng, S., Song, P."Inhibiting the NF-κB pathway enhances the antitumor effect of cabazitaxel by downregulating Bcl-2 in pancreatic cancer". International Journal of Oncology 57, no. 1 (2020): 161-170. https://doi.org/10.3892/ijo.2020.5053
Copy and paste a formatted citation
x
Spandidos Publications style
Li Z, Xuan Z, Chen J, Song W, Zhang S, Jin C, Zhou M, Zheng S and Song P: Inhibiting the NF-κB pathway enhances the antitumor effect of cabazitaxel by downregulating Bcl-2 in pancreatic cancer. Int J Oncol 57: 161-170, 2020.
APA
Li, Z., Xuan, Z., Chen, J., Song, W., Zhang, S., Jin, C. ... Song, P. (2020). Inhibiting the NF-κB pathway enhances the antitumor effect of cabazitaxel by downregulating Bcl-2 in pancreatic cancer. International Journal of Oncology, 57, 161-170. https://doi.org/10.3892/ijo.2020.5053
MLA
Li, Z., Xuan, Z., Chen, J., Song, W., Zhang, S., Jin, C., Zhou, M., Zheng, S., Song, P."Inhibiting the NF-κB pathway enhances the antitumor effect of cabazitaxel by downregulating Bcl-2 in pancreatic cancer". International Journal of Oncology 57.1 (2020): 161-170.
Chicago
Li, Z., Xuan, Z., Chen, J., Song, W., Zhang, S., Jin, C., Zhou, M., Zheng, S., Song, P."Inhibiting the NF-κB pathway enhances the antitumor effect of cabazitaxel by downregulating Bcl-2 in pancreatic cancer". International Journal of Oncology 57, no. 1 (2020): 161-170. https://doi.org/10.3892/ijo.2020.5053
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