ABSTRACT
OBJECTIVE@#To investigate the mechanism by which Chinese medicine Shengmai Yin (SMY) reverses epithelial-mesenchymal transition (EMT) through lipocalin-2 (LCN2) in nasopharyngeal carcinoma (NPC) cells CNE-2R.@*METHODS@#Morphological changes in EMT in CNE-2R cells were observed under a microscope, and the expressions of EMT markers were detected using quantitative real-time PCR (RT-qPCR) and Western blot assays. Through the Gene Expression Omnibus dataset and text mining, LCN2 was found to be highly related to radiation resistance and EMT in NPC. The expressions of LCN2 and EMT markers following SMY treatment (50 and 100 µ g/mL) were detected by RT-qPCR and Western blot assays in vitro. Cell proliferation, migration, and invasion abilities were measured using colony formation, wound healing, and transwell invasion assays, respectively. The inhibitory effect of SMY in vivo was determined by observing a zebrafish xenograft model with a fluorescent label.@*RESULTS@#The CNE-2R cells showed EMT transition and high expression of LCN2, and the use of SMY (5, 10 and 20 µ g/mL) reduced the expression of LCN2 and reversed the EMT in the CNE-2R cells. Compared to that of the CNE-2R group, the proliferation, migration, and invasion abilities of SMY high-concentration group were weakened (P<0.05). Moreover, SMY mediated tumor growth and metastasis in a dose-dependent manner in a zebrafish xenograft model, which was consistent with the in vitro results.@*CONCLUSIONS@#SMY can reverse the EMT process of CNE-2R cells, which may be related to its inhibition of LCN2 expression. Therefore, LCN2 may be a potential diagnostic marker and therapeutic target in patients with NPC.
Subject(s)
Animals , Humans , Nasopharyngeal Carcinoma/genetics , Epithelial-Mesenchymal Transition , Zebrafish , Cell Proliferation , Cell Line, Tumor , Nasopharyngeal Neoplasms/radiotherapy , Cell Movement , Gene Expression Regulation, NeoplasticABSTRACT
Shengmai Yin (SMY) is a Chinese herbal decoction that effectively alleviates the side effects of radio-therapy in various cancers and helps achieve radiotherapy's clinical efficacy.In this study,we explored the interaction mechanism among SMY,DNA methylation,and nasopharyngeal carcinoma (NPC).We identified differences in DNA methylation levels in NPC CNE-2 cells and its radioresistant cells (CNE-2R)using the methylated DNA immunoprecipitation array and found that CNE-2R cells showed genome-wide changes in methylation status towards a state of hypomethylation.SMY may restore its original DNA methylation status,and thus,enhance radiosensitivity.Furthermore,we confirmed that the dif-ferential gene Tenascin-C (TNC) was overexpressed in CNE-2R cells and that SMY downregulated TNC expression.This downregulation of TNC inhibited NPC cell radiation resistance,migration,and invasion.Furthermore,we found that TNC was hypomethylated in CNE-2R cells and partially restored to a hypermethylated state after SMY intervention.DNA methyltransferases 3a may be the key protein in DNA methylation of TNC.
ABSTRACT
A 71-year-old man was stable on warfarin (2.25 mg daily) therapy with an international normalized ratio (INR) of 1.8-2.2 after a heart valve replacement surgery. Recently, he consumed the liquid-like herbal product called shengmai-yin (10 mL daily) against medical advice. Seven days after the daily consumption of shengmai-yin, he was admitted to the intensive care unit because of consciousness disturbance [Glasgow Coma Scale (GCS) score 7] with an INR of 5.08. Head computed topography revealed intracerebral hematoma in the left temporoparietal region. Both warfarin therapy and the herbal product were withdrawn. At the same time, therapy with intravenous vitamin K1 40 mg was started. On the second day of admission, craniectomy was performed to remove the intacerebral hematoma under general anesthesia. He remained confused and restless for 2 days, but then showed progressive recovery in the consciousness level as well as motor and verbal functions. Shengmai-yin contains herbal ingredients that can interact with warfarin. The Drug Interaction Probability Scale (DIPS) indicated that warfarin and shengmai-yin were highly probable causes of intracerebral hematoma. Patients on warfarin therapy should be discouraged from taking herbal medicines, especially preparations that are already known to have antiplatelet and antithrombotic effects.
Subject(s)
Aged , Humans , Male , Anticoagulants/adverse effects , Cerebral Hemorrhage/chemically induced , Drug Interactions , Drugs, Chinese Herbal/adverse effects , Hematoma/chemically induced , Treatment Outcome , Vitamin K 1/therapeutic use , Warfarin/adverse effectsABSTRACT
A 71-year-old man was stable on warfarin (2.25 mg daily) therapy with an international normalized ratio (INR) of 1.8-2.2 after a heart valve replacement surgery. Recently, he consumed the liquid-like herbal product called shengmai-yin (10 mL daily) against medical advice. Seven days after the daily consumption of shengmai-yin, he was admitted to the intensive care unit because of consciousness disturbance [Glasgow Coma Scale (GCS) score 7] with an INR of 5.08. Head computed topography revealed intracerebral hematoma in the left temporoparietal region. Both warfarin therapy and the herbal product were withdrawn. At the same time, therapy with intravenous vitamin K1 40 mg was started. On the second day of admission, craniectomy was performed to remove the intacerebral hematoma under general anesthesia. He remained confused and restless for 2 days, but then showed progressive recovery in the consciousness level as well as motor and verbal functions. Shengmai-yin contains herbal ingredients that can interact with warfarin. The Drug Interaction Probability Scale (DIPS) indicated that warfarin and shengmai-yin were highly probable causes of intracerebral hematoma. Patients on warfarin therapy should be discouraged from taking herbal medicines, especially preparations that are already known to have antiplatelet and antithrombotic effects.