21 research outputs found
Combinational treatment of MCF-7 and MCF-7/ADR cells with EVO and DOX showed synergistic effect in reducing cell viability.
<p>MCF-7 and MCF-7/ADR cells were pretreated with different concentrations of EVO for 12 h, followed by treating with DOX for another 48 h. Cell viabilities of MCF-7 (<b>A</b>) and MCF-7/ADR (<b>C</b>) cells were measured by MTT assay. The combination index (CI) of EVO and DOX in MCF-7 (<b>B</b>) and MCF-7/ADR (<b>D</b>) cells were conducted using CalcuSyn software (Biosoft, Cambridge, UK), where CI<1 indicated synergistic effect. Data presented mean ± SE from three independent experiments conducted in triplicate.</p
Inhibition of Inhibitor of Apoptosis (IAPs) in MCF-7 and MCF-7/ADR cells by EVO.
<p>Whole-cell lysates were generated and immunoblotted with antibodies against XIAP, Survivin, cIAP1 and GAPDH. Similar results were obtained in two or three separate experiments.</p
EVO enhanced DOX-induced apoptosis in MCF-7/ADR cancer cells.
<p>MCF-7/ADR cells were pretreated with EVO (1 µM) for 12 h, and then incubated with 2 µM of Dox for another 48 h. Apoptotic measurement was Annexin V/PI assay (<b>A</b>). Data are expressed as mean ± SE of three independent experiments. * P<0.05. (<b>B</b>) The cell lysates were generated for Western blot analysis using antibodies against activated PARP, activated caspase-7, -9 and GAPDH. Examination of the combined effects of DOX and EVO on expression levels of Ras/MEK/ERK cascade (<b>C</b>) and IAPs family proteins (<b>D</b>). Similar results were obtained in three separate experiments.</p
Effects of different concentrations of EVO on the proliferation of Dox-sensitive MCF-7 (A) and Dox-resistant MCF-7/ADR (B) cells by MTT assay.
<p>The cytotoxicity caused by different concentrations of EVO in MCF-7 (<b>C</b>) and MCF-7/ADR (<b>D</b>) cells was determined by LDH assay. Each point represents the mean ± SE.</p
Inhibition of Ras/MEK/ERK signaling pathway in MCF-7 and MCF-7/ADR cells by EVO.
<p>Whole-cell lysates were generated and immunoblotted with antibodies against Ras, phosphorylated MEK (P-MEK), MEK, phosphorylated ERK (P-ERK1/2), ERK1/2 and GAPDH. Similar results were obtained in two or three separate experiments.</p
EVO sensitize the effect of DOX without inhibiting P-glycoprotein.
<p>MCF-7 (<b>A</b>) and MCF-7/ADR (<b>B</b>) cells were pretreated with EVO and Verapamil for 12 h, and then incubated Dox (2 µM) for another 4 h, then the intracellular level of Dox was determined using flow cytometry. (<b>C</b>) Effects of EVO on the expression levels of P-gp protein in MCF-7/ADR cells. After 24 h treatment of EVO and verapamil, protein levels in cell lysates were analyzed by Western blot. GAPDH was used as an internal control. Similar results were obtained in two or three separate experiments. (<b>D</b>) After 12 h treatment, the MDR pump activities were determined using a fluorimetric MDR assay kit (Abcam). Results are expressed as mean ± SE.</p
Additional file 1 of Co-delivery of dimeric camptothecin and chlorin e6 via polypeptide-based micelles for chemo-photodynamic synergistic therapy
Additional file 1: Figure S1. Particle size and PDI of PKF-Ce6 blank micelles. Figure S2. Pharmacokinetics profiles of Ce6 after administration in mice (n=3). Figure S3. H&E staining of major organs (heart, liver, spleen, lung and kidneys) collected from one mouse after treatment, scale bar is 20 μm. Table S1. Particle size of PCD micelles with different ratio of Ce6 to DCPT. Table S2. Pharmacokinetic parameters of DCPT, PCD and PPCD after administration in mice (n=3). Table S3. Pharmacokinetic parameters of Ce6, PCD and PPCD after administration in mice (n=3)
pH Triggered Size Increasing Gene Carrier for Efficient Tumor Accumulation and Excellent Antitumor Effect
High
efficiency and serum resistant capacity are important for gene carrier
in vivo usage. In this study, transfection efficiency and cell toxicity
of polyethylenimine (PEI) (branched, Mw = 25K) was remarkably improved,
when mixed with polyanion (polyethylene glycol-polyglutamic acid (PEG–PLG)
or polyglutamic acid (PLG)). Different composite orders of PEI, polyanion,
and gene, for example, PEI is first complexed with DNA, and then with
polyanion, or PEI is first complexed with polyanion, and then with
DNA, were studied. Results showed that only the polyanion/PEI complexes
exhibited additional properties, such as decreased pH, resulting in
increased particle size, as well as enhanced serum resistance capability
and improved tumor accumulation. The prepared gene carrier showed
excellent antitumor effect, with no damage on major organs, which
is suitable for in vivo gene antitumor therapy
Gold-Nanorods-Based Gene Carriers with the Capability of Photoacoustic Imaging and Photothermal Therapy
Multifunctional
nanoparticles with high gene transfection activity, low cytotoxicity,
photoacoustic imaging ability, and photothermal therapeutic properties
were prepared by conjugating low-molecular-weight polyethylenimine
onto the surfaces of gold nanorods through the formation of stable
S–Au bonded conjugates. Results revealed that the gene transfection
efficiency of the prepared polyethylenimine-modified gold nanorods
(GNRs-PEI1.8k) was higher and their cytotoxicity was less than those
of the commercial reagent PEI25k. GNRs-PEI1.8k could also be potentially
used as a photoacoustic and photothermal reagent to evaluate the pharmacokinetics,
biodistribution, and antitumor effects of gene/drug nanoparticles.
Therefore, GNRs-PEI1.8k can be considered a promising candidate for
the clinical diagnosis and treatment of tumors
Theranostic Liposomes with Hypoxia-Activated Prodrug to Effectively Destruct Hypoxic Tumors Post-Photodynamic Therapy
Photodynamic
therapy (PDT), a noninvasive cancer therapeutic method
triggered by light, would lead to severe tumor hypoxia after treatment.
Utilizing a hypoxia-activated prodrug, AQ4N, which only shows toxicity
to cancer cells under hypoxic environment, herein, a multipurpose
liposome is prepared by encapsulating hydrophilic AQ4N and hydrophobic
hexadecylamine conjugated chlorin e6 (<i>h</i>Ce6), a photosensitizer,
into its aqueous cavity and hydrophobic bilayer, respectively. After
chelating a <sup>64</sup>Cu isotope with Ce6, the obtained AQ4N-<sup>64</sup>Cu-<i>h</i>Ce6-liposome is demonstrated to be an
effective imaging probe for <i>in vivo</i> positron emission
tomography, which together with <i>in vivo</i> fluorescence
and photoacoustic imaging uncovers efficient passive homing of those
liposomes after intravenous injection. After being irradiated with
the 660 nm light-emitting diode light, the tumor bearing mice with
injection of AQ4N-<i>h</i>Ce6-liposome show severe tumor
hypoxia, which in turn would trigger activation of AQ4N, and finally
contributes to remarkably improved cancer treatment outcomes <i>via</i> sequential PDT and hypoxia-activated chemotherapy. This
work highlights a liposome-based theranostic nanomedicine that could
utilize tumor hypoxia, a side effect of PDT, to trigger chemotherapy,
resulting in greatly improved efficacy compared to conventional cancer
PDT