Effect of bortezomib in combination with cisplatin and 5-fluorouracil on 4T1 breast cancer cells

Yerlikaya, Azmi; Altıkat, Sayit; Irmak, Reyhan; Cavga, Fatma Zehra; Kocacan, Sultan Aysun; Boyaci, Ihsan

doi:10.3892/mmr.2013.1466

Cited by 18 publications

(10 citation statements)

References 15 publications

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“…The proteasome inhibitor bortezomib is a promising novel agent in the treatment of bladder cancer; however, inducible cytoprotective mechanisms may limit its potential efficacy (15). In previous studies, bortezomib has been observed to enhance the activity of cisplatin, particularly in cisplatin-resistant cells (6,8,(16)(17)(18). The present study demonstrated for the first time that cisplatin and bortezomib combined treatment induced inhibition of cell proliferation by intrinsic and extrinsic apoptotic signaling pathways in the T24 human bladder cancer cell line.…”

Section: Discussionmentioning

confidence: 65%

Synergistic effects of cisplatin and proteasome inhibitor bortezomib on human bladder cancer cells

et al. 2015

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Abstract. The proteasome inhibitor bortezomib is a promising novel agent in bladder cancer therapy; however, inducible cytoprotective mechanisms may limit its potential efficacy. To date, the cellular and molecular effects of proteasome inhibitors on bladder cancer cells have been poorly characterized. Despite the consistent rate of initial responses, cisplatin treatment typically results in the development of chemoresistance, leading to therapeutic failure. Therefore, the present study aimed to characterize the molecular mechanisms underlying the anti-proliferative effects of cisplatin and bortezomib combination therapy on the human T24 bladder cancer cell line, by analyzing the protein expression levels of apoptotic genes. Cytotoxic effects were measured using a water-soluble tetrazolium salt-1 assay, and the apoptosis-associated molecules were examined using western blot analysis and ELISA. It was observed that combined administration of cisplatin and bortezomib induced upregulation of caspase-3, -8 and -9, B-cell lymphoma-2 (Bcl-2)-like 11 and Bcl-2-interacting killer, but downregulated Bcl-2 and Bcl-extra large protein expression levels in T24 cells in a dose-dependent manner. Furthermore, enhanced protein expression of caspase-8 and -9, in line with the significantly increased caspase-3 activation, was detected when the cells were treated with a combination of cisplatin and bortezomib, compared with that of either agent alone. Bortezomib appeared to synergize with cisplatin to promote apoptosis via the extrinsic and intrinsic apoptotic pathways. Taken together, the results of the current study provide the preclinical framework for additional evaluation of the effects of combining bortezomib with other agents to induce apoptosis in bladder cancer cells.

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Section: Discussionmentioning

confidence: 65%

Synergistic effects of cisplatin and proteasome inhibitor bortezomib on human bladder cancer cells

et al. 2015

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“…We monitored the dose-response curve of cisplatin to 4T1 cells in real-time because previous studies described results with endpoint assays [41][42][43]. The half maximal inhibitory concentration (IC 50 ) values showed time dependence: 36.74 µM at 24 h, 7.608 µM at 48 h, 6.962 µM at 72 h, 4.128 µM at 96 h, and 3.995 µM at 120 h (Figure 1 and Figure S1).…”

Section: Discussionmentioning

confidence: 99%

Single Cell Mass Cytometry Revealed the Immunomodulatory Effect of Cisplatin Via Downregulation of Splenic CD44+, IL-17A+ MDSCs and Promotion of Circulating IFN-γ+ Myeloid Cells in the 4T1 Metastatic Breast Cancer Model

Balog

Hackler²,

Kovács³

et al. 2019

IJMS

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The treatment of metastatic breast cancer remained a challenge despite the recent breakthrough in the immunotherapy regimens. Here, we addressed the multidimensional immunophenotyping of 4T1 metastatic breast cancer by the state-of-the-art single cell mass cytometry (CyTOF). We determined the dose and time dependent cytotoxicity of cisplatin on 4T1 cells by the xCelligence real-time electronic sensing assay. Cisplatin treatment reduced tumor growth, number of lung metastasis, and the splenomegaly of 4T1 tumor bearing mice. We showed that cisplatin inhibited the tumor stroma formation, the polarization of carcinoma-associated fibroblasts by the diminished proteolytic activity of fibroblast activating protein. The CyTOF analysis revealed the emergence of CD11b+/Gr-1+/CD44+ or CD11b+/Gr-1+/IL-17A+ myeloid-derived suppressor cells (MDSCs) and the absence of B220+ or CD62L+ B-cells, the CD62L+/CD4+ and CD62L+/CD8+ T-cells in the spleen of advanced cancer. We could show the immunomodulatory effect of cisplatin via the suppression of splenic MDSCs and via the promotion of peripheral IFN-γ+ myeloid cells. Our data could support the use of low dose chemotherapy with cisplatin as an immunomodulatory agent for metastatic triple negative breast cancer.

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“…There are several preclinical and clinical studies indicating that the drug combinations tested in our study have potential for the treatment of LC patients. Bortezomib potentiates the effect of cisplatin in different cancer cell types [ 26 , 27 ] and induces apoptosis in cisplatin-resistant SCLC cells [ 28 ]. The combination of bortezomib with radiation therapy and cisplatin was shown in a phase I trial to be safe for treatment of head and neck cancer patients [ 29 ].…”

Section: Discussionmentioning

confidence: 99%

Synergistic effects of combining proteasome inhibitors with chemotherapeutic drugs in lung cancer cells

et al. 2017

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BackgroundThe prognosis for patients with disseminated lung cancer is poor and current treatments have limited survival benefit as resistance often occurs, and is often associated with significant toxicity. A possible strategy to improve treatment and evade chemoresistance may be to find new combinations of drugs. The aim of this study was to analyze the potential of combining proteasome inhibitors (PIs) with chemotherapeutic drugs used in the routine treatment for lung cancer patients.ResultsThe median-effect method was applied to the Fluorometric Microculture Cytotoxicity Assay (FMCA) to evaluate effects of combining two different PIs (bortezomib and b-AP15) with clinically used chemotherapeutic drugs representing different mechanisms of action (cisplatin, gefitinib, gemcitabine and vinorelbine) in two lung cancer cell lines (one sensitive and one resistant). Proteasome inhibition in combination with cisplatin, gemcitabine or vinorelbine had synergistic effects in at least one of the tested cell lines. Furthermore, the effect of gefitinib appeared strongly potentiated by the PI in the least resistant lung cancer cell line, although the level of synergy could not be determined with the median-effect method.ConclusionsCombining PIs with cisplatin, gefitinib, gemcitabine or vinorelbine show potential as new combination chemotherapy for the treatment of lung cancer.Electronic supplementary materialThe online version of this article (10.1186/s13104-017-2842-z) contains supplementary material, which is available to authorized users.

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Effect of bortezomib in combination with cisplatin and 5-fluorouracil on 4T1 breast cancer cells

Cited by 18 publications

References 15 publications

Synergistic effects of cisplatin and proteasome inhibitor bortezomib on human bladder cancer cells

Synergistic effects of cisplatin and proteasome inhibitor bortezomib on human bladder cancer cells

Single Cell Mass Cytometry Revealed the Immunomodulatory Effect of Cisplatin Via Downregulation of Splenic CD44+, IL-17A+ MDSCs and Promotion of Circulating IFN-γ+ Myeloid Cells in the 4T1 Metastatic Breast Cancer Model

Synergistic effects of combining proteasome inhibitors with chemotherapeutic drugs in lung cancer cells

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