<p>Oridonin overcomes the gemcitabine resistant PANC-1/Gem cells by regulating GST pi and LRP/1 ERK/JNK signalling</p>

Abstract

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.

<p>Saikosaponin D Inhibits Proliferation and Promotes Apoptosis Through Activation of MKK4–JNK Signaling Pathway in Pancreatic Cancer Cells</p>

“…30 Oridonin can overcome gemcitabine resistance in PANC1/ Gem cells by regulating GSTπ and LRP1-ERK-JNK signaling, inducing cell apoptosis. 31 Our previous results have also demonstrated that cryptotanshinone and imatinib have a cooperative role in inducing cell apoptosis, suggesting a combination therapy for the treatment of chronic myeloid leukemia patients. 32 In this study, we proved that SSD was effective in the induction of apoptosis and activation of the MKK4-JNK pathway in pancreatic cancer cells.…”

<p>Phillygenin, a MELK Inhibitor, Inhibits Cell Survival and Epithelial–Mesenchymal Transition in Pancreatic Cancer Cells</p>

“…The existing literature has already documented good anti-tumor effects with more than 50 kinds of TCM in the treatment of PC, like oblongifolin C, oridonin, and Wumei. [31][32][33] PHI is a phenylethanoid glycoside isolated from the Chinese medicinal Osmanthus fragrans flower, which has been proven to have various pharmacological properties, such as anti-oxidation, hypolipidemic inhibition, and inhibition of low-density lipoprotein oxidation. 34,35 However, the mechanism of PHI-mediated anti-tumor action has not been fully elucidated.…”

LINC00680 Modulates Docetaxel Resistance in Breast Cancer via miR-320b/CDKL5 Axis

“…In vitro experiments suggested that knockdown of CDKL5 and LINC00680 decreased the expression of MDR1, MRP5 and LRP1 (Fig. 4), which are known as drugresistance genes in various cancers [30][31][32][33]. The role of MDR1 and MRP7 in docetaxel resistance were demonstrated in different types of cancer [34][35][36][37].…”