Objective To investigate the radiosensitizing effect of 17AAG-cypate micelles on human non-small cell lung cancer A549 cells and its possible mechanism.Methods (1) A single-hit multi-target model formula was used to analyze the radiosensitizing effects of 17AAG-M and 17AAG-cypate-M.(2) The effects of 17AAG-cypate-M on the viability of A549 cells under laser and X-ray irradiation were analyzed by MTT assay.(3) The effect of the drugs on the cell senescence was observed by β-galactosidase staining assay.(4) The effects of different treatment conditions on DNA damage repair were analyzed by γ-H2AX immunofluorescence staining assay.(5) The expression of p-Erk1/2 and p-Akt was measured by Western blot.The paired t test was used for analyzing the differences between groups.Results Compared with the X-ray irradiation group,the X-ray+17AAG-cypate-M group had a lower mean lethal dose and a sensitization enhancement ratio greater than 1,indicating that 17AAG-cypate-M had a radiosensitizing effect.Compared with the 17AAG-M group,the 17AAG-cypate-M group showed significantly lower cell viability (P<0.01),a significantly higher percentage of aging cells (P<0.01),and significantly further delayed DNA damage repair (P<0.01).And the 17AAG-cypate-M group had lower expression of p-Erk1/2 and p-Akt than the 17AAG-M group.Conclusions Compared with 17AAG-M,17AAG-cypate-M has a higher radiosensitizing effect on A549 cells.The mechanism might be inducing the cell senescence,delaying DNA damage repair,and inhibiting the expression of p-Erk1/2 and p-Akt.

OBJECTIVE: Our previous study revealed many genes differentially expressed in human laryngeal squamous cell carcinoma tissues (LSCC) and related adjacent normal tissues. We verificated the differentiated expressions of target genes, possibly related to LSCC. And these results can be foundations of further study of these target genes function. METHOD: SENP1, CD109, Laminin alpha 2, Laminin alpha 3 were selected according to the cDNA microarray results. The expression of these genes mRNA and protein were detected by RT-PCR and Western blot in 12 cases of LSCC and related adjacent normal tissues. RESULT: The mRNA expression of SENP1, CD109 and Laminin alpha 3 were significantly higher while Laminin alpha 2 were significantly lower in LSCC tissues than in corresponding adjacent normal tissues by Semiquantitative RT-PCR. Western blot analysis revealed SENP1, CD109 protein expression were significantly higher in LSCC tissues than in corresponding adjacent normal tissues. CONCLUSION SENP1, CD109, Laminin alpha 2 and Laminin alpha 3 may correlated with tumorigenesis and development of LSCC and can provide beneficial clue for study pathogenesis of LSCC in molecular level.
Aged ; Aged, 80 and over ; Antigens, CD ; genetics ; Carcinoma, Squamous Cell ; genetics ; Cysteine Endopeptidases ; Endopeptidases ; genetics ; GPI-Linked Proteins ; genetics ; Gene Expression Regulation, Neoplastic ; Humans ; Laminin ; genetics ; Laryngeal Neoplasms ; genetics ; Male ; Middle Aged ; Neoplasm Proteins ; genetics ; Oligonucleotide Array Sequence Analysis

Co-delivery of chemotherapeutics and immunostimulant or chemoimmunotherapy is an emerging strategy in cancer therapy. The precise control of the targeting and release of agents is critical in this methodology. This article proposes the asynchronous release of the chemotherapeutic agents and immunostimulants to realize the synergistic effect between chemotherapy and immunotherapy. To obtain a proof-of-concept, a co-delivery system was prepared

Atherosclerosis (AS) is a lipid-driven chronic inflammatory disease occurring at the arterial subendothelial space. Macrophages play a critical role in the initiation and development of AS. Herein, targeted codelivery of anti-miR 155 and anti-inflammatory baicalein is exploited to polarize macrophages toward M2 phenotype, inhibit inflammation and treat AS. The codelivery system consists of a carrier-free strategy (drug-delivering-drug, DDD), fabricated by loading anti-miR155 on baicalein nanocrystals, named as baicalein nanorods (BNRs), followed by sialic acid coating to target macrophages. The codelivery system, with a diameter of 150 nm, enables efficient intracellular delivery of anti-miR155 and polarizes M1 to M2, while markedly lowers the level of inflammatory factors and . In particular, intracellular fate assay reveals that the codelivery system allows for sustained drug release over time after internalization. Moreover, due to prolonged blood circulation and improved accumulation at the AS plaque, the codelivery system significantly alleviates AS in animal model by increasing the artery lumen diameter, reducing blood pressure, promoting M2 polarization, inhibiting secretion of inflammatory factors and decreasing blood lipids. Taken together, the codelivery could potentially be used to treat vascular inflammation.