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Platinum anti-tumor drugs are currently the most widely used first-line chemotherapeutic drugs in clinical practice, and their curative effects are remarkable. However, the problems of platinum drug resistance in non-small cell lung cancer, breast cancer, ovarian cancer and others seriously limit effectiveness and clinical application of platinum drugs. The occurrence of platinum drug resistance is caused by many factors. At present, the resistance mechanism of platinum drugs mainly includes the following aspects: decreasing the accumulation of platinum in cells, increasing the inactivation of platinum in cells, repairing DNA damage and tumor cell apoptosis inactivation. This article reviews the drug resistance mechanism and coping strategy of platinum anti-tumor drugs, providing ideas for the development of platinum anti-tumor drugs and references for overcoming clinical platinum drug resistance.
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OBJECTIVE：To preliminarily s tudy the potential mechanism of astragaloside Ⅳ on allergic rhinitis （AR）model mice. METHODS ：C57/BL6 mice were randomly divided into blank group ，model group and astragaloside Ⅳ group，with 10 mice in each group. Except for blank group ，AR model was prepared by sensitization and challenge with ovalbumin on day 0，7，14 and 21-27. Astragaloside Ⅳ group was given astragaloside Ⅳ 40 mg/kg intraperitoneally at the dose of 0.02 mL/g on the 15th to 27th day of modeling （given the drug 1 h before challenge sensitization on the 21st to 27th day ）. Blank group and model group were given constant volume of normal saline intraperitoneally ，once a day. Twenty-four hours after sensitization from the last challenge ， the infiltration of inflammatory cells in the nasal mucosa of each group was observed ，and the contents of interleukin 4（IL-4）， IL-5 and interferon gamma （IFN-γ）in the nasal lavage fluid were measured. The levels of reactive oxygen species （ROS），and the count of phosphorylated Janus kinase 2（p-JAK2）and phosphorylation signal transduction and activation of transcription protein 6 （p-STAT6）positive cells in the nasal mucosa and spleen as well as the phosphorylation levels of JAK 2 and STAT 6 proteins in spleen tissue （i.e. p-JAK 2/JAK2 ratio，p-STAT6/STAT6 ratio）were also determined. RESULTS ：Compared with blank group ，the number of inflammatory cells in the nasal mucosa （eosinophils and mast cells ）in the model group ，the contents of IL- 4 and IL- 5 in the nasal lavage fluid ，and the levels of ROS in the nasal mucosa and spleen tissues in the model group ，the count of p-JAK 2 and p-STAT 6 positive cells increased significantly ，the p-JAK2/JAK2 ratio，p-STAT6/STAT6 ratio in the spleen tissue were significantly increased （P＜0.05），and the content of INF-γ in the nasal lavage fluid was significantly decreased（P＜0.05）. Compared with model group ，the count of inflammatory cells infiltrated in the nasal mucosa ，the contents of IL- 4 and IL- 5 in the nasal cavity lavage fluid ，the level of ROS and the number of p-JAK 2 and p-STAT 6 positive cellsin the nasal mucosa and spleen tissue as well as the p-JAK2/JAK2 ratio and p-STAT 6/STAT6 ratio in spleen tissue were decreased significantly （P＜0.05），and the content of INF-γ in nasal lavage fluid was significantly increased（P＜0.05）. CO NCLUSIONS：Astragaloside Ⅳ can effectively improve the inflammatory response in AR model mice ，the mechanism of which may be related to down-regulation of JAK2/STAT6 signaling pathway and ROS level.
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Objective@#To observe the effect of Yiqi Wenyang Decoction on the infiltration and activation of NK cells in nasal mucosa of mouse model with allergic rhinitis (AR), and to explore the potential mechanism for effective intervention of AR with Yiqi Wenyang Decoction.@*Methods@#Fourty-eight mice were randomly divided into blank group, model group, low, medium and high dose of Yiqi Wenyang Decoction group and Cetirizine group, with 8 rats in each group. After modeling of AR, the model group was filled with 0.9% sodium chloride solution. Yiqi Wenyang Decoction groups of each dose were given different concentrations of Yiqi Wenyang Decoction water extract, while the Cetirizine group was given aqueous solution of Cetirizine. The behavior, morphological changes of nasal mucosa and infiltration of NK cells in nasal mucosa were observed. The levels of IL-4 and INF-γ in nasal lavage fluid were measured. Besides, the drug safety was observed by acute toxicity test.@*Results@#In the respect of behavioral scoring, middle and high dose of Yiqi Wenyang Decoction group were superior to the model group (number of sneezing: q value was 7.189, 8.748, respectively; number of scratching nose: q value was 12.074, 14.560, respectively; all P<0.05). In middle and high dose of Yiqi Wenyang Decoction group, the infiltration of NK cells and nasal lavage fluid IL-4 levels were lower than those in model group (IOD: q value was 10.073, 12.322, respectively; IOD/Area: q value was 10.954, 14.073, respectively; IL-4: q value was 4.705, 6.801, respectively; all P<0.05). There was no significant difference in nasal lavage fluid of INF-γ among each group (Fv=1.166, P>0.05). In acute toxicity test, no obvious poisoning symptoms and death occurred in mice.@*Conclusion@#Yiqi Wenyang Decoction can control the nasal symptom, reduce the local NK cell infiltration of nasal mucosa and inhibit the expression of the 2-type cytokines released by NK cells, which may be related with the potential mechanism of effective intervention of AR with Yiqi Wenyang Decoction.
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OBJECTIVE@#To investigate the mechanism.@*METHOD@#We isolate the mouse bone marrow cells and cultured with rGM-CSF and rIL-4 to stimulate bone marrow cells to transfer to immature dendritic cells. And then the immature dendritic cells were costimulated with ILPS and different concentrations of Bimingan Granule.@*RESULT@#MHC II, CD80, CD86 were detected by flow cytometer and TNF-alpha, IL-1beta, IL-6 and IL-10 were quantified by ELISA.@*CONCLUSION@#Our results showed that Bimingan Granule may significantly inhibit the differentiation of immature dendritic cells to mature dendritic cells.