Journal: Breast Cancer Research : BCR

Article Title: Novel sorafenib analogues induce apoptosis through SHP-1 dependent STAT3 inactivation in human breast cancer cells

doi: 10.1186/bcr3457

Figure Lengend Snippet: SHP-1-dependent inhibition of STAT3 mediates the apoptotic effects of SC-1 and SC-43 in breast cancer cells. A , inhibition of SHP-1 reverses effects of SC-1 and SC-43 on apoptosis. MDA-MB-468 cells were pretreated with 50 μM sodium vanadate, a non-specific phosphatase inhibitor (Left), or 50 μM PTP inhibitor III, a specific SHP-1 inhibitor (Right), for 60 minutes and then treated with SC-1 or SC-43 at 7.5 μM for 36 hours. B , silencing SHP-1 by siRNA reduces the effects of SC-1 and SC-43 on p-STAT3 inhibition and apoptosis in MDA-MB-453 and MDA-MB-468 cells. Cells were transfected with control siRNA (scrambled) or SHP-1 siRNA for 48 hours then treated with SC-1 or SC-43 at 7.5 μM for another 24 hours. C , effects of sorafenib, SC-1 and SC-43 on SHP-1 expression and phosphorylation (Tyr536 and Ser591). MDA-MB-468 cells were exposed to sorafenib, SC-1 or SC-43 at 7.5 μM for 36 hours. Western blot data are representative of three independent experiments. D , the activity of SHP-1 (Upper) and SHP-2 (Lower) in drug-treated MDA-MB-468 cells. Cells were treated with sorafenib, SC-1 or SC-43 at 7.5 μM for 36 hours and cell lysates were assayed for phosphatase activity as described in Methods. E , dose-escalation effects of SC-43 on the activity of SHP-1 (Upper) and SHP-2 (Lower) in drug-treated MDA-MB-468 cells. Cells were treated with SC-43 at the indicated doses for 36 hours. F , effect of SC-43 on SHP-1 activity in drug-treated HCC-1937, MDA-MB-231, MCF-7, MDA-MB-453 and SK-BR3 cells (Upper); cells were treated with SC-43 at 10 μM for 36 hours. Effects of sorafenib, SC-1 and SC-43 on phosphatase activity in recombinant SHP-1 protein (Lower). Recombinant SHP-1 protein (25 ng) was incubated with drugs at 100 nM for 30 minutes. For bar charts, Columns, mean; bars, SD ( n = 3). * P <0.05.

Article Snippet: Sodium vanadate and specific SHP-1 inhibitor were purchased from Cayman Chemical (Ann Arbor, MI, USA).

Techniques: Inhibition, Transfection, Expressing, Western Blot, Activity Assay, Recombinant, Incubation

Journal: Breast Cancer Research : BCR

Article Title: Novel sorafenib analogues induce apoptosis through SHP-1 dependent STAT3 inactivation in human breast cancer cells

doi: 10.1186/bcr3457

Figure Lengend Snippet: Therapeutic evaluation of SC-1 and SC-43 on breast cancer xenograft tumor growth in vivo . A , SC-1 and SC-43 show significant antitumor effects on MDA-MB-468 tumors. Growth curves of MDA-MB-468 tumors treated with vehicle, sorafenib, SC-1 and SC-43. Points, mean (n = 6); bars, SE. B , left, western blot analysis of p-STAT3 and STAT3 in MDA-MB-468 tumors. Right, the activity of SHP-1 in MDA-MB-468 tumors. Tumors were harvested 28 days after treatment and assayed for molecular events by western blotting and for SHP-1 activity. Columns, mean; bars, SD (n = 3). * P <0.05. C , overexpressed STAT3 in MDA-MB-468 tumors shows a significant protective effect against treatment with SC-43. Left , p-STAT3 and STAT3 expressions in STAT3-overexpressed and in empty vector- transfected MDA-MB-468 cells. Middle , growth curves of STAT3-overexpressed MDA-MB-468 tumors treated with vehicle and SC-43. Points, mean (n = 6); bars, SE. Right, western blot analysis of p-STAT3 and STAT3 in STAT3-overexpression MDA-MB-468 tumors treated with vehicle or SC-43. Tumors were harvested 28 days after treatment and assayed for molecular events by western blotting. D , body weight of xenograft mice bearing MDA-MB-468 tumors (left) and STAT3-overexpression MDA-MB-468 tumors (right) during the in vivo experiment. Points, mean (n = 6); bars, SE. Female NCr athymic nude mice (four to six weeks of age) were used for experiments (A) to (D). Mice were treated with sorafenib, SC-1 or SC-43 (10 mg/kg body weight) per os daily. Controls received vehicle. E , scheme of SHP-1 mediated drug mechanism of SC-1 and SC-43 in breast cancer cells.

Article Snippet: Sodium vanadate and specific SHP-1 inhibitor were purchased from Cayman Chemical (Ann Arbor, MI, USA).

Techniques: In Vivo, Western Blot, Activity Assay, Plasmid Preparation, Transfection, Over Expression

Journal: Breast Cancer Research : BCR

Article Title: Novel sorafenib analogues induce apoptosis through SHP-1 dependent STAT3 inactivation in human breast cancer cells

doi: 10.1186/bcr3457

Figure Lengend Snippet: Immunohistochemical stain for p-STAT3 and SHP-1 in a clinical sample. Representative immunohistochemical patterns showing (A) strong nuclear expression with no cytoplasmic expression for STAT3 in cancer cells, (B) no nuclear expression with mild cytoplasmic expression for SHP-1 in cancer cells, (C) neither nuclear expression nor cytoplasmic expression for STAT3 in adjacent normal breast tissue, and (D) no nuclear expression and strong cytoplasmic expression for SHP-1 in adjacent normal breast tissue.

Article Snippet: Sodium vanadate and specific SHP-1 inhibitor were purchased from Cayman Chemical (Ann Arbor, MI, USA).

Techniques: Immunohistochemical staining, Staining, Expressing

Journal: Journal of Nanobiotechnology

Article Title: Pro-efferocytic macrophage membrane biomimetic nanoparticles for the synergistic treatment of atherosclerosis via competition effect

doi: 10.1186/s12951-022-01720-2

Figure Lengend Snippet: Characterizations of MM@Lips-SHP1i NPs: A TEM image of macrophage membrane vesicles; B TEM image of blank liposomes; C TEM image of MM@Lips-SHP1i; D Hydrodynamic diameters of Lips, Lips-SHP1i, MM, MM@Lips and MM@Lips-SHP1i; E Zeta potential of SHP1i, Lips, Lips-SHP1i, MM, MM@Lips and MM@Lips-SHP1i; F UV–vis absorption spectra of SHP1i, Lips, Lips-SHP1i, MM, MM@Lips and MM@Lips-SHP1i; G The size stability of MM@Lips-SHP1i NPs over a span of 7 days in PBS and H in 10% mouse serum. I Representative AS-related protein bands of Lips-SHP1i (I), macrophages (II), macrophage membranes (III) and MM@Lips-SHP1i (IV) using western blotting

Article Snippet: Thus, to further improve the treatment effect of macrophage biomimetic nanoparticles, a SHP1 inhibitor (SHP1i) was loaded in liposome.

Techniques: Membrane, Liposomes, Zeta Potential Analyzer, Western Blot

Journal: Journal of Nanobiotechnology

Article Title: Pro-efferocytic macrophage membrane biomimetic nanoparticles for the synergistic treatment of atherosclerosis via competition effect

doi: 10.1186/s12951-022-01720-2

Figure Lengend Snippet: A Quantification of oxLDL removal with a fixed amount of oxLDL (60 μg) while varying the amount of added MM@Lips; B Quantification of oxLDL removal with a fixed amount of MM@Lips (0.5 mg) while varying the amount of added oxLDL; C Quantification of LPS removal with a fixed amount of LPS (50 ng) while varying the amount of added MM@Lips; D Quantification of LPS removal with a fixed amount of MM@Lips (0.5 mg) while varying the amount of added LPS; E The proportion of Oil Red O staining area in RAW264.7 cells after diferent treatments (** P < 0.01, *** P < 0.001); F Intracellular TC value of RAW264.7 cells after diferent treatments (*** P < 0.001); G Western blotting was used to detect the scavenger receptor expression changes on RAW264.7 cells after different treatments (I: Control, II: oxLDL, III: SHP1i, IV: Lips-SHP1i, V: MM@Lips, VI: MM@Lips-SHP1i); H Quantification of CD36 and SRA relative expression levels (** P < 0.01, *** P < 0.001)

Article Snippet: Thus, to further improve the treatment effect of macrophage biomimetic nanoparticles, a SHP1 inhibitor (SHP1i) was loaded in liposome.

Techniques: Staining, Western Blot, Expressing, Control

Journal: Journal of Nanobiotechnology

Article Title: Pro-efferocytic macrophage membrane biomimetic nanoparticles for the synergistic treatment of atherosclerosis via competition effect

doi: 10.1186/s12951-022-01720-2

Figure Lengend Snippet: A The hemolysis of PC (positive control), NC (negative control), SHP1i (I), Lips-SHP1i (II), MM@Lips (III) and MM@Lips-SHP1i (IV) to mouse red blood cells (DI water as a positive control and saline as a negative control); B Mouse blood panel and serum biochemistry analysis before (0d, control) and after injection of MM@Lips-SHP1i for 1, 7, 21d; C H&E staining of collected organs including the heart, liver, spleen, lungs, kidneys of healthy mice after injected with MM@Lips-SHP1i at 1, 7 and 21 d and control mice (scale bar: 200 μm)

Article Snippet: Thus, to further improve the treatment effect of macrophage biomimetic nanoparticles, a SHP1 inhibitor (SHP1i) was loaded in liposome.

Techniques: Positive Control, Negative Control, Saline, Control, Injection, Staining