RNA interference-mediated gene silencing of cyclophilin A enhances the radiosensitivity of PAa human lung adenocarcinoma cells in vitro

Abstract

Radiotherapy is currently the major therapeutic strategy for patients with lung cancer. However, radioresistance and various side effects continue to present challenging issues for this form of treatment. A recent study demonstrated that cyclophilin A (CyPA) was overexpressed in non-small cell lung cancer and, therefore, presents a novel potential therapeutic target. In addition, gene-radiotherapy is a novel method for cancer treatment. Therefore, the objective of the present study was to investigate the potential effect of CyPA silencing on radiosensitivity in human lung adenocarcinoma in vitro. The stable CyPA-silencing lung adenocarcinoma (PAa) cell line was generated using lentivirus-mediated small hairpin RNAs. The knockdown of CyPA was determined using fluorescent microscopy and western blot analysis. Cells were irradiated using various doses of cobalt-60 (0, 2, 4, 6 and 8 Gy). The radiosensitizing effects were determined by a clonogenic survival assay. Apoptosis and cell cycle distribution were evaluated using flow cytometry. Silencing of CyPA significantly increased the apoptosis of PAa cells. In addition, the radiosensitivity of cells was markedly enhanced following CyPA silencing. Furthermore, silencing of CyPA, in combination with irradiation, induced G2/M phase cell cycle arrest. Taken together, the data suggest that the silencing of CyPA, combined with radiation therapy, may increase the therapeutic efficacy of lung cancer treatment through regulation of the cell cycle and apoptosis-associated signaling pathways.

Novel Cyclophilin Inhibitor Decreases Cell Proliferation and Tumor Growth in Models of Hepatocellular Carcinoma

“…The importance of cyclophilins in the G 1 /S transition has also been observed in HCC [ 20 , 21 , 22 ]. Alternatively, Jiang et al [ 40 ] reported a G 2 /M arrest due to a CypA knockdown in lung adenocarcinoma cells. Indeed, the NV651 treatment caused an early accumulation of cells in the G 2 /M phase of the cell cycle.…”

Knockdown of SMAD3 inhibits the growth and enhances the radiosensitivity of lung adenocarcinoma via p21 in vitro and in vivo

“…Yang et al recently reported that long noncoding RNA LINC00483 regulates the radiosensitivity of lung adenocarcinoma by interacting with the microRNA-144/HOXA10 signaling axis [12]. Jiang et al demonstrated that RNA interference-mediated gene silencing of cyclophilin A markedly enhanced the radiosensitivity of PAa human lung adenocarcinoma cells in vitro and induced G2/M phase cell cycle arrest [13]. Dong et al showed that speckle-type POZ protein affected DNA damage response repair kinetics, apoptosis, and cell cycle checkpoints to regulate the response of lung adenocarcinoma cells to radiation [14].…”

Cyclophilin A/CD147 Interaction: A Promising Target for Anticancer Therapy

“…Activation of the CypA/CD147 interaction inhibits the apoptosis of cancer cells [ 13 , 54 , 75 , 76 , 77 , 78 , 79 , 80 , 81 ]. The antiapoptotic effects are associated with the upregulation of the PI3K/AKT/mTOR signaling pathway, modulation of the Bcl-2 family, and inhibition of caspase cascades [ 13 , 54 , 78 , 79 ].…”

“…Overexpression of CypA prevents hypoxia- and cisplatin-induced apoptosis in several cancer cell lines, including prostate cancer cells [ 56 ]. CypA is significantly upregulated after radiation therapy in lung adenocarcinoma cells, and CypA inhibition greatly increases radiosensitivity, reinforcing cell apoptosis [ 80 ]. CD147 is highly expressed in human epidermal growth factor receptor 2 (HER2)-positive breast cancer tissues, and its suppression enhances the anticancer efficacy of trastuzumab by increasing apoptosis in breast cancer cells [ 81 ].…”