Bortezomib (PS-341, Velcade) increases the efficacy of trastuzumab (Herceptin) in HER-2–positive breast cancer cells in a synergistic manner

Cardoso, Fátima; Durbecq, Virginie; Laes, Jean-François; Badran, Bassam; Lagneaux, Laurence; Bex, Françoise; Desmedt, Christine; Willard-Gallo, Karen; Ross, Jeffrey S.; Burny, Arsène; Piccart, Martine; Sotiriou, Christos

doi:10.1158/1535-7163.mct-06-0104

Cited by 58 publications

(44 citation statements)

References 40 publications

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“…18 In other reports, several sequential combination procedures had been used. Examples include addition of the first drug for 24 h followed by the second drug for a further 48 h, 26 treatment of the first drug for 24 h followed by its removal and addition of the second drug for a further 48 h, 27 targeted therapy for 72 h followed by chemo treatment for 24 h or chemo treatment for 24 h followed by targeted therapy for 48 h, 28 and the first drug for 24 h followed by a second single or add-on drug for 24 h. 29,30 Different means of administration of the drugs may affect the anti-proliferative outcome. Here we used PAC-1 treatment for 48 h and Cis treatment for 24 h (72 h total).…”

Section: Discussionmentioning

confidence: 99%

Synergistic antitumor activity of pro‐apoptotic agent PAC‐1 with cisplatinum by the activation of CASP3 in pulmonary adenocarcinoma cell line H1299

Huang

Liang

Zhang

et al. 2015

Asia-Pac J Clncl Oncology

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Aim: Evasion of apoptosis is a hallmark of human cancer cells. We sought to explore the potential synergistic antitumor activity and underlying mechanisms of the pro-apoptotic agent PAC-1 plus cisplatinum (Cis) in non-small cell lung cancer (NSCLC) cell lines. Methods: The adenocarcinoma cell lines H1299, A549, PC9, H1650 and H1975 were used as in vitro models. Colorimetric MTT assays, Western blotting and flow cytometry were used to evaluate the antigrowth effects of PAC-1 and/or Cis and apoptosis status. The activated form of CASP3 (C-CASP3) was assessed by immunofluorescent staining. Results: Single-agent Cis and PAC-1 were able to inhibit the cancer cell growth in certain dose ranges, with IC 50 values of 1.9-11.7 and 5.6-14.8 μM, respectively. Sequential Cis→PAC-1 or concurrent Cis + PAC-1, but not PAC-1→Cis combinations showed synergistic effects on cell growth inhibition in H1299 cells (combination index, CI ≤ 0.6). In contrast, other combination modes mostly showed seemingly antagonistic effects (CI > 1.0). Flow cytometric analysis showed that Cis→PAC-1 sequential combination showed strong proapoptotic effects in H1299 cells. Western blots showed that in H1299, PC9 and H1975 cells, PAC-1 promoted the C-CASP3, but only in H1299 cells was there a synergistic effect with Cis on the CASP3 activation. Conclusions: PAC-1 showed anti-tumor activity in NSCLCs in vitro and a synergistic effect with cisplatin in EGFR wt KRAS wt H1299 cells. Our data suggest a potential treatment approach using cisplatin plus a pro-apoptotic agent acting via CASP3 activation for this subgroup of pulmonary adenocarcinomas.

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Section: Discussionmentioning

confidence: 99%

Synergistic antitumor activity of pro‐apoptotic agent PAC‐1 with cisplatinum by the activation of CASP3 in pulmonary adenocarcinoma cell line H1299

Huang

Liang

Zhang

et al. 2015

Asia-Pac J Clncl Oncology

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“…Second, according to recent study and the disappointing results of clinical trials using bortezomib as monotherapy in some solid tumours, it appears that this molecule should be used in combination. In 2006, Cardoso et al (2006) showed a synergy between bortezomib and trastuzumab in HER2/neu þ þ þ / þ þ cell lines. These results convinced the authors to conduct a phase 1 clinical trial that aimed at evaluating this drug combination.…”

Section: Discussionmentioning

confidence: 99%

Validation of UBE2C protein as a prognostic marker in node-positive breast cancer

et al. 2009

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BACKGROUND:We recently identified and validated UBE2C RNA as a prognostic marker in 252 node-positive (N þ ) breast cancers by means of a microarray study. The aim of this study was to validate UBE2C protein as a prognostic marker in N þ breast cancer by immunohistochemistry (IHC). METHODS: To this end, 92 paraffin-embedded blocks were used. The impact of UBE2C IHC value on metastasis-free survival (MFS) and overall survival (OS) was evaluated and compared with Ki-67 and Nottingham prognostic index (NPI) performances. RESULTS: In accordance with genomic data, UBE2C IHC had a significant impact both on MFS and OS (hazard ratio ¼ 6.79 -P ¼ 0.002; hazard ratio ¼ 7.14 -P ¼ 0.009, respectively). Akaike information criterion proved that the prognostic power of UBE2C IHC was stronger than that of Ki-67 (and close to that of NPI). Furthermore, multivariate analyses with NPI showed that, contrary to Ki-67 IHC, UBE2C IHC remained an independent factor, both for MFS (adjusted P ¼ 0.02) and OS (adjusted P ¼ 0.04). CONCLUSION: We confirmed that UBE2C protein measured by IHC could be used as a prognostic marker in N þ breast cancer. The potential predictive interest of UBE2C as a marker of proteasome activity needs further investigations.

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“…11,12 In the meantime, combination of bortezomib with various agents, such as dexamethasone, DNA-damaging drugs, trastuzumab (herceptin) and tipifarnib, have been widely investigated. 13,14 It seems that bortezomib offers great promise to overcome resistance to conventional chemotherapy. 15 More recently, bortezomib was shown to interact synergistically with cyclin-dependent kinase inhibitor flavopiridol and histone deacetylase inhibitor suberoylanilide hydroxamic acid or sodium butyrate to induce apoptosis in Bcr-Abl þ cells.…”

Section: Introductionmentioning

confidence: 99%

Arsenic trioxide and proteasome inhibitor bortezomib synergistically induce apoptosis in leukemic cells: the role of protein kinase Cδ

et al. 2007

Leukemia

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Arsenic trioxide (ATO) and proteasome inhibitor bortezomib have been successfully applied to treat acute promyelocytic leukemia (APL) and multiple myeloma (MM), respectively. Their synergistic effects with other anticancer drugs have been widely studied. Here, we investigated the potential synergy of bortezomib and ATO on Bcr-Abl þ leukemic K562 cells. The results showed that cotreatment of bortezomib at 32 nM, a half concentration for growth arrest, and ATO at 1 lM, a dose with no significant cytotoxic effect, synergistically induced apoptosis in the cell line, followed by enhanced mitochondrial dysfunction, release of cytochrome c and apoptosis-inducing factor, caspase-3 cleavage and degradation of poly-adenosine diphosphate-ribose polymerase together with the decreased Bcr-Abl protein. These two drugs synergistically induced proteolytic activation of protein kinase Cd (PKCd) with enhanced activation of two mitogen-activated protein kinases phospho-c-Jun NH 2 -terminal kinase and p38. The specific PKCd inhibitor rottlerin markedly decreased bortezomib plus ATO-induced apoptosis, suggesting that PKCd plays an important role in bortezomib plus ATO-induced apoptosis. Moreover, apoptosis synergy of bortezomib and ATO could also be seen in some kinds of acute leukemic cell lines and primary cells. Totally, our results indicate that combined regimen of bortezomib and ATO might be a potential therapeutic remedy for the treatment of leukemia.

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Bortezomib (PS-341, Velcade) increases the efficacy of trastuzumab (Herceptin) in HER-2–positive breast cancer cells in a synergistic manner

Cited by 58 publications

References 40 publications

Synergistic antitumor activity of pro‐apoptotic agent PAC‐1 with cisplatinum by the activation of CASP3 in pulmonary adenocarcinoma cell line H1299

Synergistic antitumor activity of pro‐apoptotic agent PAC‐1 with cisplatinum by the activation of CASP3 in pulmonary adenocarcinoma cell line H1299

Validation of UBE2C protein as a prognostic marker in node-positive breast cancer

Arsenic trioxide and proteasome inhibitor bortezomib synergistically induce apoptosis in leukemic cells: the role of protein kinase Cδ

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