The C2min aptamer-modified gene delivery system for targeting ADPC/AIPC prostate cancer / 药学实践杂志

Objective To synthesize a novel prostate cancer targeting gene vector PAMAM-PEG-C2min and improve gene transfection efficiency targeting on prostate cancer. Methods The aptamer (C2min) and polyamide-amine (PAMAM) were ligated by polyethylene glycol (PEG). The structure of the synthesized PAMAM-PEG-C2min was identified by NMR. The biological characteristics of the nanoparticles were examined by the uptake experiments and gene transfection experiments (the loaded gene was siR-M) with the prostate cancer cells (PC3 and LNCaP). Besides, the in vivo targeting was investigated using in vivo image system. The in vivo targeting results indicated that PAMAM-PEG-C2min can achieve the simultaneous targeting of two prostate cancer tissues. Results The PAMAM-PEG-C2min synthesis was confirmed by NMR. Cell uptake experiments showed that the cell uptake efficiency of PAMAM-PEG-C2min was concentration dependent. In vitro experiments showed that the PC3 and LNCaP cells transfection efficiency and targeting of PAMAM-PEG modified with C2min were significantly improved compared with the PEG modified PAMAM. Conclusion PAMAM-PEG-C2min is a potential targeted drug delivery vehicle. It provides a new technology platform for comprehensive and specific targeting treatment of prostate cancer.

The novel long noncoding RNA LOC283070 is involved in the transition of LNCaP cells into androgen-independent cells via its interaction with PHB2 / 亚洲男科学杂志(英文版)

We sought to investigate the underlying mechanism of action of the long noncoding RNA (lncRNA) LOC283070 in the development of androgen independence in prostate cancer. The interactions between LOC283070 and target proteins were investigated by RNA pull-down and RNA-binding protein immunoprecipitation (RIP) assays. Subcellular fractionation and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) were used to detect the subcellular localization of LOC283070. Western blotting was performed to detect the expression of prohibitin 2 (PHB2). Luciferase activity assays were performed to evaluate the effects of LOC283070 and PHB2 on the androgen receptor (AR) signaling pathway. A methyl thiazolyl tetrazolium (MTT) assay and a growth curve assay were used to test cell viability. Flow cytometry was performed to analyze cell cycles. A transwell assay was employed to test cell migration. We identified PHB2 as an interaction partner of LOC283070 in the pull-down and RIP experiments. Furthermore, we confirmed that the enrichment of LOC283070 with PHB2 in androgen-independent LNCaP (LNCaP-AI) cells was much greater than that in LNCaP cells. Moreover, the expression of PHB2 was not significantly different between the two cell lines, and the expression of LOC283070 in the nuclei of the LNCaP-AI cells was significantly greater than that in the LNCaP cells. In vitro data revealed that PHB2 overexpression significantly inhibited AR activity and cell proliferation and migration and induced accumulation of prostate cancer cells in G0/G1 phase. Moreover, the overexpression of LOC283070 fully abrogated the effects of PHB2 overexpression. In conclusion, we found that LOC283070 can bind to PHB2 located in the nucleus and inhibit its effect, and this is one of the mechanisms by which LOC283070 is involved in the transition of LNCaP cells into androgen-independent cells.

The novel long noncoding RNA LOC283070 is involved in the transition of LNCaP cells into androgen-independent cells via its interaction with PHB2 / 亚洲男科学杂志(英文版)

We sought to investigate the underlying mechanism of action of the long noncoding RNA (lncRNA) LOC283070 in the development of androgen independence in prostate cancer. The interactions between LOC283070 and target proteins were investigated by RNA pull-down and RNA-binding protein immunoprecipitation (RIP) assays. Subcellular fractionation and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) were used to detect the subcellular localization of LOC283070. Western blotting was performed to detect the expression of prohibitin 2 (PHB2). Luciferase activity assays were performed to evaluate the effects of LOC283070 and PHB2 on the androgen receptor (AR) signaling pathway. A methyl thiazolyl tetrazolium (MTT) assay and a growth curve assay were used to test cell viability. Flow cytometry was performed to analyze cell cycles. A transwell assay was employed to test cell migration. We identified PHB2 as an interaction partner of LOC283070 in the pull-down and RIP experiments. Furthermore, we confirmed that the enrichment of LOC283070 with PHB2 in androgen-independent LNCaP (LNCaP-AI) cells was much greater than that in LNCaP cells. Moreover, the expression of PHB2 was not significantly different between the two cell lines, and the expression of LOC283070 in the nuclei of the LNCaP-AI cells was significantly greater than that in the LNCaP cells. In vitro data revealed that PHB2 overexpression significantly inhibited AR activity and cell proliferation and migration and induced accumulation of prostate cancer cells in G0/G1 phase. Moreover, the overexpression of LOC283070 fully abrogated the effects of PHB2 overexpression. In conclusion, we found that LOC283070 can bind to PHB2 located in the nucleus and inhibit its effect, and this is one of the mechanisms by which LOC283070 is involved in the transition of LNCaP cells into androgen-independent cells.