The relationship among oridonin, miR-200b-3p and pancreatic cancer on epithelial-to-mesenchymal transition (EMT) was investigated for the molecular mechanism or signaling pathways on the migration in pancreatic cancer. BxPC-3 and PANC-1 cells were cultivated and the IC50 of oridonin in BxPC-3 and PANC-1 cells were obtained by the CCK-8 array. The expression of miR‑200b-3p was verified by using real-time PCR and its target gene was predicted. BxPC-3 and PANC-1 cells were treated with oridonin or transfected by miR-200b-3p, those cells were used for western blot assay, Transwell assay, ELISA, immunofluorescence staining, tumorigenesis assay in nude mice and immunohistochemical assay to verify the effects of oridonin or miR-200b-3p on pancreatic cancer. We found that oridonin inhibited the proliferation of BxPC-3 and PANC-1 cells in a dose-dependent manner. miR-200b-3p was downregulated by oridonin in BxPC-3 and PANC-1 cells. ZEB1 was a target gene for miR-200b-3p. Oridonin or overexpression of miR‑200b-3p can inhibit the cell migration in BxPC-3 and PANC-1 cells. miR-200b-3p can inhibit the EMT and oridonin can inhibit the expression of ZEB1, N-cadherin and fibronectin but not increase the expression of E-cadherin, while the cell adhesion molecules ICAM-1 and VCAM-1 were decreased by oridonin in BxPC-3 and PANC-1 cells and the cytoskeleton was altered by oridonin in PANC-1 cells compared with the control. In summary, the results demonstrate that miR‑200b-3p was able to inhibit the EMT of human pancreatic cancer in vivo and in vitro by targeted ZEB1. In vitro, oridonin had a certain effect on the migration in BxPC-3 and PANC-1 cells, but not though type III EMT by miR-200-3p/ZEB1 axis, and may be related to type Ⅱ EMT, tumor microenvironment or altering the cytoskeleton. In vivo, oridonin inhibited the cancer migration in the nude mouse model though inhibiting EMT.
Background: Chemotherapy remains a primary treatment method for advanced pancreatic cancer. However, chemotherapy resistance can influence the therapeutic effect of pancreatic cancer. The resistance mechanism of chemotherapeutic agents such as gemcitabine, which is an agent typically used to treat pancreatic cancer, is complicated and can be influenced by genes and the environment. Oridonin is a tetracyclic diterpenoid compound extracted from the traditional Chinese herb Rabdosia labtea . Oridonin may overcome drug resistance in pancreatic cancer, but researching pancreatic cancer drug resistance of chemotherapy by oridonin is not completely understood. Purpose: The present study aimed to assess the impact of oridonin on multidrug resistance proteins, apoptosis-associated proteins and energy metabolism in gemcitabine-resistant PANC-1 (PANC-1/Gem) pancreatic cancer cells. Methods: Gemcitabine resistance in PANC-1/Gem cells was induced using a concentration gradient of gemcitabine. Cell Counting Kit-8 assays were used to detect the impact of gemcitabine and oridonin on the proliferation of PANC-1 and PANC-1/Gem cells. Western blot analysis and immunofluorescence were used to detect the expression of multidrug resistance proteins, apoptosis-associated proteins and low-density lipoprotein receptor protein 1 (LRP1) proteins in PANC-1/Gem cells. The effects of gemcitabine and oridonin on PANC-1/Gem cells apoptosis were detected using flow cytometry. Animal xenograft tumor assays were used to detect the effect of gemcitabine and oridonin on pancreatic cancer in vivo. Furthermore, the ATP Assay kit was used to determine the effects of gemcitabine and oridonin on ATP levels in PANC-1/Gem cells. Immunofluorescence assays were used to detect the effects of gemcitabine and oridonin on the expression of low-density lipoprotein receptor protein 1 (LRP1) in PANC-1/Gem cells. In addition, LRP1 expression was knocked down in PANC-1/Gem cells via lentiviral vector-mediated RNA silencing. Clone formation assays and Western blot analysis were used to detect the effect of LRP1 knockdown on the proliferation of PANC-1/Gem cells. Results: The present results demonstrate that oridonin overcomes PANC-1/Gem cells gemcitabine reistance by regulating GST pi and LRP1/ERK/JNK signaling. Conclusion: In conclusion, the present study indicated that oridonin could overcome gemcitabine resistance in PANC-1/Gem cells by regulating GST pi and LRP1/ ERK/JNK signaling, inducing cell apoptosis. Therefore, oridonin with gemcitabine may be a promising preoperative treatment for patients who suffer from pancreatic cancer.
As a stand‐alone therapy strategy may not be sufficient for effective cancer treatment and a combination of chemotherapy with other therapies is a main trend in cancer treatment. A combination of chemotherapy and photothermal therapy (PTT) is reported here to achieve the goal of cascade multistage cancer treatment. A thermally responsive amphiphilic copolymer is designed and then a CuS nanoparticles (NPs)‐based carbon monoxide (CO) photoinduced release system and doxorubicin (Dox) are encapsulated to construct the nanomedicine. The large‐sized nanomedicine can accumulate in tumors after long circulation in vivo and will generate heat to act as a photothermal therapeutic agent by near infrared (NIR) light. Moreover, synergically release of CO and Dox is achieved and acted as a sensitized chemotherapeutic agent. The combination of PTT and chemotherapy sensitization can effectively eliminate active tumor cells in the periphery of the tumor. CuS NPs are also released after the degradation of nanomedicine and small‐sized CuS NPs possess better tumor penetration and achieve penetration‐enhanced PTT by further NIR irradiation, thereby effectively eliminating tumor cells inside solid tumors. Hence, cascade multistage cancer treatment of “combined PTT and chemotherapy sensitization”—“penetration‐enhanced PTT” is achieved, and tumor cells are comprehensively and effectively eliminated.
the changes in personal awareness of protection during the COVID-19 pandemic. Methods: This retrospective study included patients tested for influenza virus A and B from November 2017 to March 2021 at the Affiliated People's Hospital of Ningbo University (Ningbo, China). Influenza virus A and B tested by direct RT-PCR. A small group of 100 regular participants in influenza virus detection were surveyed on the use of protective measures in four different influenza seasons.
Fluorescence sensing organophosphorus pesticides (OPs) has been of great importance for both food safety and global environment, however, the reported fluorescent probes are usually directly exposed to the external environment,...
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