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Low-dose taxotere enhances the ability of sorafenib to induce apoptosis in gastric cancer models.

Tesei A, Leonetti C, Zupi G, Scarsella M, Brigliadori G, Ulivi P, Fabbri F, Arienti C, Amadori D, Passardi A, Silvestrini R, Zoli W - J. Cell. Mol. Med. (2011)

Bottom Line: Apoptosis induction was associated with caspase-3 and -9 activation and mitochondrial membrane depolarization.This synergism was probably due to the induction of an anomalous multidiploid G0-G1 peak and to consequent mitotic catastrophe, which increased sensitivity to sorafenib.Consistent with in vitro results, the docetaxel-sorafenib sequence exhibited high therapeutic efficacy in NCI-N87 mouse xenografts producing tumour weight inhibition (> 65%), tumour growth delay (up to 25 days) and increased mouse survival (30%).

View Article: PubMed Central - PubMed

Affiliation: Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Meldola, Italy. anna.tesei@irst.emr.it

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(A) Western blot analysis of baseline expression of sorafenib targets (c-raf, b-raf, EGFR, PDGFR-β, VEGFR) in gastric cancer lines, and κ-ras mutation analysis (mut., mutated; w.t., wild-type). (B) Cytotoxic activity of sorafenib after 24, 48 and 72-hr exposure in gastric cancer cell lines. (C) Effect of 10 μM sorafenib concentration on MAP kinase pathway after 48-hr exposure.
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fig01: (A) Western blot analysis of baseline expression of sorafenib targets (c-raf, b-raf, EGFR, PDGFR-β, VEGFR) in gastric cancer lines, and κ-ras mutation analysis (mut., mutated; w.t., wild-type). (B) Cytotoxic activity of sorafenib after 24, 48 and 72-hr exposure in gastric cancer cell lines. (C) Effect of 10 μM sorafenib concentration on MAP kinase pathway after 48-hr exposure.

Mentions: Cell lines were characterized by different molecular profiles. All cell lines expressed c-raf, b-raf and PDGF receptor β. VEGF receptor expression was found in AKG, KKP and NCI-N87 cells, while the expression of EGF receptor was only present in the last two. k-ras mutation analysis revealed gene alterations in GK2, KKP and NCI-N87 cells (Fig. 1A).


Low-dose taxotere enhances the ability of sorafenib to induce apoptosis in gastric cancer models.

Tesei A, Leonetti C, Zupi G, Scarsella M, Brigliadori G, Ulivi P, Fabbri F, Arienti C, Amadori D, Passardi A, Silvestrini R, Zoli W - J. Cell. Mol. Med. (2011)

(A) Western blot analysis of baseline expression of sorafenib targets (c-raf, b-raf, EGFR, PDGFR-β, VEGFR) in gastric cancer lines, and κ-ras mutation analysis (mut., mutated; w.t., wild-type). (B) Cytotoxic activity of sorafenib after 24, 48 and 72-hr exposure in gastric cancer cell lines. (C) Effect of 10 μM sorafenib concentration on MAP kinase pathway after 48-hr exposure.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3822798&req=5

fig01: (A) Western blot analysis of baseline expression of sorafenib targets (c-raf, b-raf, EGFR, PDGFR-β, VEGFR) in gastric cancer lines, and κ-ras mutation analysis (mut., mutated; w.t., wild-type). (B) Cytotoxic activity of sorafenib after 24, 48 and 72-hr exposure in gastric cancer cell lines. (C) Effect of 10 μM sorafenib concentration on MAP kinase pathway after 48-hr exposure.
Mentions: Cell lines were characterized by different molecular profiles. All cell lines expressed c-raf, b-raf and PDGF receptor β. VEGF receptor expression was found in AKG, KKP and NCI-N87 cells, while the expression of EGF receptor was only present in the last two. k-ras mutation analysis revealed gene alterations in GK2, KKP and NCI-N87 cells (Fig. 1A).

Bottom Line: Apoptosis induction was associated with caspase-3 and -9 activation and mitochondrial membrane depolarization.This synergism was probably due to the induction of an anomalous multidiploid G0-G1 peak and to consequent mitotic catastrophe, which increased sensitivity to sorafenib.Consistent with in vitro results, the docetaxel-sorafenib sequence exhibited high therapeutic efficacy in NCI-N87 mouse xenografts producing tumour weight inhibition (> 65%), tumour growth delay (up to 25 days) and increased mouse survival (30%).

View Article: PubMed Central - PubMed

Affiliation: Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Meldola, Italy. anna.tesei@irst.emr.it

Show MeSH
Related in: MedlinePlus