Abstract
The use of ionizing radiation (IR) during radiotherapy can induce malignant effects, such as metastasis, which contribute to poor prognoses in lung cancer patients. Here, we explored the ability of dendrobine, a plant-derived alkaloid from Dendrobium nobile, to improve the efficacy of radiotherapy in non-small cell lung cancer (NSCLC). We employed Western blotting, quantitative real-time (qRT)-PCR, transwell migration assays, and wound-healing assays to determine the effects of dendrobine on the migration and invasion of A549 lung cancer cells in vitro. Dendrobine (5 mm) inhibited γ-irradiation-induced migration and invasion of A549 cells by suppressing sulfatase2 (SULF2) expression, thus inhibiting IR-induced signaling. To investigate the inhibitory effects of dendrobine in vivo, we established a mouse model of IR-induced metastasis by injecting BALB/c nude mice with γ-irradiated A549 cells via the tail vein. As expected, injection with γ-irradiated cells increased the number of pulmonary metastatic nodules in mice (0 Gy/DPBS, 9.8 ± 1.77; 2 Gy/DPBS, 20.87 ± 1.42), which was significantly reduced with dendrobine treatment (2 Gy/Dendrobine, 10.87 ± 0.71), by prevention of IR-induced signaling. Together, these findings demonstrate that dendrobine exerts inhibitory effects against γ-irradiation-induced invasion and metastasis in NSCLC cells in vitro and in vivo at non cytotoxic concentrations. Thus, dendrobine could serve as a therapeutic enhancer to overcome the malignant effects of radiation therapy in patients with NSCLC.
Highlights
Lung cancer is the most common cause of cancer-related death, due to its high rate of metastasis [1]
10 Gy of ionizing radiation (IR) promoted the invasion of A549 cells, whereas this effect was decreased by treatment with 5 μm dendrobine (Figure 2c)
These findings indicate that dendrobine inhibits IR-induced migration and invasion in A549 lung cancer cells
Summary
Lung cancer is the most common cause of cancer-related death, due to its high rate of metastasis [1]. Despite recent improvements in diagnostic technologies, approximately 70% patients with NSCLC are diagnosed at an advanced stage with metastatic disease [2]. Studies have reported that IR can induce cancer cell migration and invasion in multiple types of cancer cell and animal models [5,6,7]. These IR-induced properties can cause malignant effects, such as local recurrence and distant metastasis, by increasing metastatic potential, leading to poor prognoses in cancer patients [8]. New strategies that inhibit IR-induced cancer cell migration, invasion, and metastasis are needed to improve the therapeutic effects of IR
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