Fewer than 20% of patients diagnosed with pancreatic cancer can be treated with surgical resection. The effects of proton beam irradiation were evaluated on the cell viabilities in Panc-1 and Capan-1 pancreatic cancer cells. The cells were irradiated with proton beams at the center of Bragg peaks with a 6-cm width using a proton accelerator. Cell proliferation was assessed with the MTT assay, gene expression was analyzed with semi-quantitative or quantitative reverse transcription-polymerase chain reaction analyses and protein expression was evaluated by western blotting. The results demonstrated that Capan-1 cells had lower cell viability than Panc-1 cells at 72 h after proton beam irradiation. Furthermore, the cleaved poly (ADP-ribose) polymerase protein level was increased by irradiation in Capan-1 cells, but not in Panc-1 cells. Additionally, it was determined that histone H2AX phosphorylation in the two cell lines was increased by irradiation. Although a 16 Gy proton beam was only slightly up-regulated cyclin-dependent kinase inhibitor 1 (p21) protein expression in Capan-1 cells, p21 expression levels in Capan-1 and Panc-1 cells were significantly increased at 72 h after irradiation. Furthermore, it was observed that the expression of DNA repair protein RAD51 homolog 1 (RAD51), a homogenous repair enzyme, was decreased in what appeared to be a dose-dependent manner by irradiation in Capan-1 cells. Contrastingly, the transcription of survivin in Panc-1 was significantly enhanced. The results suggest that RAD51 and survivin are potent markers that determine the therapeutic efficacy of proton beam therapy in patients with pancreatic cancer.

arctigenin is a natural lignan that is found in burdock with anti-viral, -oxidative, -inflammatory and anti-tumor activities. in the current study, the effect of arctigenin on metastatic potential was examined in 4T-1 mouse triple-negative breast cancer cells. The results indicated that arctigenin inhibited cell motility and invasiveness, which was determined using wound healing and transwell invasion assays. arctigenin suppressed matrix metalloprotease-9 (MMP-9) activity via gelatin zymography, and protein expression of cyclooxygenase-2 (coX-2) and MMP-3. Furthermore, arctigenin attenuated the mrna expression of metastatic factors, including MMP-9, MMP-3 and coX-2. Based on these results, the effect of arctigenin on the mitogen-activated protein kinase (MaPK)/activating protein-1 (aP-1) signaling pathway was assessed in an attempt to identify the regulatory mechanism responsible for its anti-metastatic effects. arctigenin was demonstrated to inhibit the phosphorylation of extracellular signal-regulated protein kinase (erK) and c-Jun n-terminal kinase (JnK), and the nuclear translocations of the aP-1 subunits, c-Jun and c-Fos. in summary, the present study demonstrated that in 4T-1 mouse triple-negative breast cancer cells the anti-metastatic effect of arctigenin is mediated by the inhibition of MMP-9 activity and by the inhibition of the metastasis-enhancing factors MMP-9, MMP-3 and coX-2, due to the suppression of the MaPK/aP-1 signaling pathway. The results of the current study demonstrated that arctigenin exhibits a potential for preventing cell migration and invasion in triple negative breast cancer.

Chemotherapy failure is often caused by drug resistance, for which no effective treatment strategy has been established. Many studies have been undertaken with the aim of overcoming drug resistance using natural products. Arctigenin (ATG), a natural product, has been investigated for its anti‐cancer effects in HER2‐overexpressing, ER‐positive, and triple‐negative breast cancer cells. We investigated the efficacy of ATG against self‐established doxorubicin (DOX)‐resistant breast cancer cells (MCF‐DR and MDA‐DR cells) derived from MCF‐7 and MDA‐MB‐231 cells, respectively. ATG was found to increase DOX intracellular levels by downregulating multidrug Resistance 1 (MDR1) mRNA expression in DOX‐resistant cells. In addition, combined treatment with DOX and ATG (DOX/ATG) reduced the viability of and colony formation by DOX‐resistant cells. DOX/ATG also significantly induced G2/M cell cycle arrest by suppressing the Cyclin D1/CDK4/RB pathways and suppressed the expressions of MDR1 and Cyclin D1 by inhibiting the Mitogen‐activated protein kinase (MAPK)/Activating protein‐1 (AP‐1) signaling pathways. Furthermore, DOX/ATG induced DNA damage and attenuated the expressions of RAD51 and Ku80. However, PARP1 (Poly [ADP‐ribose] polymerase1) cleavage and AIF (Apoptosis‐inducing factor) induced apoptosis did not occur despite DNA damage‐induced cell death. Rather, flow cytometry showed that DOX/ATG caused necrosis. In summary, DOX/ATG increased intracellular DOX levels by inhibiting MDR1 and inducing G2/M arrest by inhibiting the Cyclin D1/CDK4/RB pathways and causing necrosis by damaging DNA. Our results suggest that ATG might be used as an adjuvant to enhance the efficacy of DOX in DOX‐resistant breast cancer.