ABSTRACT
RNA interference (RNAi) has been proved as a novel approach for gene therapy. However, RNAi mono-therapy only aims at single gene, it therefore may ultimately fail to cure cancers caused by polygene variation. To overcome the deficiency of RNAi mono-therapy, "combinatorial RNA interference" (coRNAi) was put forward as a new strategy. By co-expressing the inducers of RNAi triggering single or multiple targets directly and other RNA- or protein-based silencers, coRNAi keeps target genes silent, prevents carcinogenic progression and induces apoptosis of tumor cells. This paper mainly reviews the major strategies of coRNAi and their applications in cancer gene therapy.
Subject(s)
Animals , Humans , Apoptosis , Genetic Therapy , Methods , MicroRNAs , Genetics , Neoplasms , Genetics , Pathology , Therapeutics , Oncogenes , RNA Interference , RNA, Small Interfering , Genetics , RNA, Small Nuclear , GeneticsABSTRACT
High mobility group A2 protein (HMGA2), an architectural factor, is highly expressed in various cancer types including lung cancers. It is a candidate target for cancer therapy. RNAi is an effective gene silencing method with low cost and less time-consuming. It is possible to exploit this technology in therapy. Here, 5 siRNAs targeting Hmga2 gene (HMGA2 siRNA1-5) were designed and synthesized. MTT assay, colony formation assay, transwell assay and flow cytometry were used to evaluate the effects of these siRNAs on lung cancer cell lines (NCI-H446 and A549). Results from cell proliferation, clone formation, migration and apoptosis showed that HMGA2 siRNA1, 3, 5 could affect these aspects for both lung cancer cell lines. Among the five siRNAs, HMGA2 siRNA5 showed the greatest inhibition effects. The inhibition effects of HMGA2 siRNA5 are sequence specific and are not due to the induction of interferon response. Taken together, siRNAs targeting Hmga2 gene are potential candidates for lung cancer gene therapy.
Subject(s)
Humans , Apoptosis , Cell Line, Tumor , Cell Movement , Cell Proliferation , Colony-Forming Units Assay , Gene Silencing , Genetic Therapy , HMGA2 Protein , Genetics , Metabolism , Interferons , Metabolism , Lung Neoplasms , Genetics , Metabolism , Pathology , Point Mutation , RNA, Messenger , Metabolism , RNA, Small Interfering , Genetics , TransfectionABSTRACT
<p><b>OBJECTIVE</b>Measure the thermal stability and the forming constant of inclusion complex for paeonol with beta-CD, and investigate interaction between beta-CD and paeonol,</p><p><b>METHOD</b>The thermal stability investigated by using different thermal analysis. The forming constant was determined by using phase method.</p><p><b>RESULT</b>Comparing with melt temperature of paeonol, that of its inclusion complex increase about 220 degrees C. The solubility of paeonol increases with the increased concentration of beta-CD, the composing ratio and the inclusion constant of beta-CD-paeonol is respectively 1/1 and 27.42 mL x mg(-1).</p><p><b>CONCLUSION</b>Inclusion constant is applied to research the stability of included drug in physiological condition.</p>