To study the chemosensitivity and the mechanisms of recombinant adenovirus vector expressing ING4 and IL-24 (Ad-ING4-IL-24) on lung adenocarcinoma in vitro and in vivo, the expression of ING4 and IL-24 in A549 cells was detected by RT-PCR and Western blotting. The growth inhibition, apoptosis rate and apoptosis body were measured by MTT, flow cytometry and Hoechst staining respectively. For in vivo study, we first established the A549 tumor model by grafting A549 cells in athymic nude mice; and then injected Ad-ING4-IL-24 into the tumors. Two weeks after injection, we killed the mice, removed the tumors, weighted and calculated the ratios of tumor-suppression. We also detected the expressions of ING4, IL-24, bax, bcl-2, VEGF with immunohistochemistry. The results indicated that ING4 and IL-24 were proved successfully transcription and expression in A549 cells. More interestingly, the joint group inhibited the growth of A549 cells and induced apoptosis. The in vivo data showed that the joint group suppressed the tumor growth conspicuously through up-regulating the expression of bax, and down-regulating the expression of bcl-2, VEGF. The study proved that Ad-ING4-IL-24 significantly enhanced the chemosensitivity to anticancer drug DDP in lung adenocarcinoma, which may related with cell apoptosis and antiangiogenesis.
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Int J Biol Macromol
March 2024
Department of Thoracic Surgery, the First Affiliated Hospital of Soochow University, Suzhou 215006, China.
Poor systemic administration capability, a natural tendency to target CAR-positive cells, nonspecific shedding to normal organs, and poor viral persistence in tumor tissues are major hindrances to the therapeutic benefit of adenovirus (Ad) gene vectors in the clinical setting. Antheraea pernyi silk fibroin (ASF) grafted with targeted peptides was used to coat ING4-IL-24 dual-gene coexpressing adenovirus for targeted gene therapy of lung carcinoma. The dual-gene vector with a diameter of 390 nm could target and infect H460 lung tumor cells, internalize into cells, express the ING4 and IL-24 genes at a high level, effectively inhibit the proliferation of lung tumor cells, and induce their apoptosis.
View Article and Find Full Text PDFPolymers (Basel)
October 2021
National Engineering Laboratory for Modern Silk, Department of Textile Engineering, College of Textile and Clothing Engineering, Soochow University, Suzhou 215123, China.
One of the major challenges for lung cancer gene therapy is to find a gene delivery vector with high efficiency and low toxicity. In this study, low-molecular-weight polyethyleneimine (PEI, 1.8 kDa) was grafted onto the side chains of silk fibroin (BSF) to prepare cationized BSF (CBSF), which was used to package the plasmid DNA (pDNA) encoded by the inhibitor of growth 4 (ING4) and interleukin-24 (IL-24).
View Article and Find Full Text PDFNanomedicine (Lond)
April 2021
National Engineering Laboratory for Modern Silk, College of Textile & Clothing Engineering, Soochow University, Industrial Park, Suzhou, 215123, Jiangsu, China.
To obtain a gene carrier that can effectively deliver loaded therapeutic genes to tumor cells, avoid toxic effects on normal cells and reduce nonspecific adsorption of plasma proteins. The conjugate of poly(ethylene glycol) (PEG) and MMP2SSP (PEG-MMP2SSP) was covalently coupled to cationized silk fibroin (CASF) through disulfide bond exchange reaction to obtain a PEG-MMP2SSP-modified CASF (CASFMP). The PEG chains were effectively cleaved from the CASFMP by MMP2.
View Article and Find Full Text PDFInt J Nanomedicine
March 2020
Department of Oncology, First Affiliated Hospital of Soochow University, Suzhou 215006, People's Republic of China.
Introduction: Cancer gene therapy requires both effective tumor suppressor genes and safe vectors that express target genes efficiently. Inhibitor of growth 4 (ING4) inhibits tumor growth via multiple pathways. Interleukin-24 (IL-24) also has tumor-suppressive activity against a broad spectrum of human cancers.
View Article and Find Full Text PDFThe construction of a targeted gene delivery system with low cytotoxicity to normal tissues is an urgent need for the clinical treatment of liver cancer. In this study, silk fibroin (ASF) was cationized with low-molecular-weight polyethylenimine (PEI, 1.8 kDa) to synthesize a cationized silk fibroin (CASF).
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