Inhibition of lung tumor growth in nude mice by siRNACD31 targeting PECAM-1

Abstract

Small interfering RNA (siRNA) provides a promising therapeutic approach in the silencing of disease-causing genes. In the present study, the use of 2′-O-methyl-modified siRNA-cluster of differentiation 31 (siRNACD31), with cationic liposome RNA interference (RNAi)-mate as a carrier, effectively silenced the platelet endothelial cell molecule 1 (PECAM-1) gene of murine hemangioendothelioma cells in vitro. In vivo, 2′-O-methyl-modified siRNACD31 carried by RNAi-mate was successfully delivered, targeting the PECAM-1 gene in the vasculature of nude mouse lung carcinoma xenografts. The growth of the lung carcinoma xenografts was inhibited by the 2′-O-methyl-modified siRNACD31 and RNAi-mate complexes, and the expression of the PECAM-1 protein was downregulated, with a simultaneous decrease in vascular endothelial growth factor (VEGF) protein in the lung carcinoma xenografts. 2′-O-methyl-modified siRNACD31-RNAi-mate complexes may provide a potential therapeutic strategy in lung carcinoma treatment. The effect of PECAM-1 on VEGF expression may possibly be attributed to the function of PECAM-1 signal transduction.

Targeting platelet/endothelial cell adhesion molecule 1 enhances cisplatin sensitivity of human nasopharyngeal carcinoma cells exposed to ionizing radiation

“…Collectively, these results suggested that PECAM -1 might be an attractive target for cancer therapy and an important regulator in determining drug resistance of tumor cells after ionizing irradiation. This notion was also supported by recent studies showing that the growth of mantle cell lymphoma in a xenograft model was associated with upregulated PECAM-1 expression (27) and that PECAM-1 siRNA inhibited tumor growth in a lung carcinoma xenograft model (28) . It was assumed that reduced PECAM-1 expression might attenuate the activities of several pro-survival pathways involving PECAM-1 signaling complexes, such as Bcl-2 family proteins, PI3K/ Akt, pathway, and NF-kB activity.…”

Identification of protein targets in cerebral endothelial cells for brain arteriovenous malformation (AVMs) molecular therapies

“…PECAM-1 is a diagnostic membrane protein used to demonstrate the presence of endothelial cells in histological tissues [ 40 , 42 ]. It is also expressed in certain tumours, which can imply a rapidly growing tumour because of its involvement in angiogenesis, for this reason PECAM-1 has been used as an angiogenic target in cancer therapies [ 5 , 25 ]. Previous in vitro studies in human and animal cell cultures showed that PECAM-1 expression increased when endothelial cells were exposed to irradiation doses from 10 to 20 Gy [ 11 ].…”

MiR-31 modulates coelomocytes ROS production via targeting p105 in Vibrio splendidus challenged sea cucumber Apostichopus japonicus in vitro and in vivo

“…These agomirs were then dissolved into RNasefree water to obtain a working solution of 20 mM. We mixed 10 mL of each agomir or siRNA with 10 mL of siRNA-MateTM transfection reagent (GenePharma, Shanghai) and 80 mL of PBS to serve as the transfection solution [25,26]. Twenty sea cucumbers (60 ± 10 g)…”