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Article in Chinese | WPRIM | ID: wpr-906189


Objective:To explore the potential targets and related mechanism involved in the paclitaxel resistance to ovarian cancer. Method:Ovarian cancer A2780 cells and A2780 paclitaxel-resistant cells (A2780/T) were treated by 2, 4, 8, 16, 32, 64, 128, 256 μmol·L<sup>-1</sup> paclitaxel (PTX) for 24 h or 48 h respectively <italic>in vitro</italic>. The proliferation rate of A2780 cells and A2780/T cells treated with paclitaxel was determined by methyl thiazolyl tetrazolium (MTT) colorimetric method assay. A2780 and A2780/T cells were analyzed by LC-MS/MS Label-Free quantitative proteomics to identify and screen differentially expressed proteins in the two groups of cells. Gene ontology (GO) annotation and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis were used to determine the potential biomarkers of paclitaxel resistance in ovarian cancer. Conventionally cultured A2780 cells were used as a control group, and A2780/T cells were treated with 0, 1, 4 μmol·L<sup>-1</sup> PTX. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) and Western blot methods were used to detect and verify the mRNA and protein expression levels of potential target transforming growth factor-<italic>β</italic>-activated kinase 1 binding protein 1 (TAB1) and its downstream related molecules transforming growth factor-<italic>β</italic>-activated kinase (TAK1) and p38. Result:After PTX treatment for 24 h and 48 h, the cell viability of A2780 and A2780/T cells decreased. The inhibitory rate of PTX on A2780 cells was significantly higher than that of A2780/T cells. In A2780 cells, the IC<sub>50</sub> of PTX treatment for 48 h was 0.002 μmol·L<sup>-1</sup>, while in A2780/T cells, the IC<sub>50 </sub>of PTX was greater than the maximum concentration of 128 μmol·L<sup>-1</sup>, indicating that A2780/T cells were resistant to PTX compared with A2780 cells. 441 differentially expressed proteins and 421 special differentially expressed proteins between A2780/T and A2780 cells were screened by label-free quantitative proteomic analysis. GO function enrichment analysis showed that the binding proteins accounted for the majority (80%) among the differentially expressed proteins. According to the results of KEGG pathway analysis and expression site analysis, TAB1 might be a potential biomarker in paclitaxel-resistant ovarian cancer. Compared with A2780 cells, mRNA and protein expression levels of TAB1 in A2780/T cells were significantly reduced (<italic>P</italic><0.01). mRNA expression of TAK1 and p38 that interacted with TAB1 were also significantly reduced (<italic>P</italic><0.05, <italic>P</italic><0.01), while there was no significant change in protein expression. Conclusion:TAB1 may be a potential biomarker of paclitaxel resistance to ovarian cancer , and its mechanism may be related to the TAB1/TAK1/p38 MAPK pathway.

Acta Pharmaceutica Sinica ; (12): 274-282, 2021.
Article in Chinese | WPRIM | ID: wpr-872620


Seventy-nine injectable herb extractions have been approved by the Chinese Food and Drug Administration (CFDA) and are frequently administered intravenously for various diseases. Unfortunately, herb-drug interactions are under-investigated and sometimes overlooked in the clinic. In the present investigation the in vitro inhibition of 9 drug metabolizing enzymes including CYP1A, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A was assessed using an appropriate probe substrate for each enzyme with human liver microsomes. Metabolite formation was quantified using a validated and sensitive high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay. The IC50 of each herb extract was estimated using a concentration range from 5% to 0.5%, and the time-dependent inhibition of the nine CYP450 isoenzymes was also determined. Of the 79 approved iv herb injectables, 37 inhibited CYP1A, 24 inhibited CYP2A6, 41 inhibited CYP2B6, 36 inhibited CYP2C8, 31 inhibited CYP2C9, 41 inhibited CYP2C19, 13 inhibited CYP2D6, 25 inhibited CYP2E1, and 42 inhibited CYP3A with 50% or greater inhibition at a test concentration of 5% (v/v). IC50 differences were noted between pre-incubation or co-incubation assays with HLM for 30 min, with the time-dependent inhibitory (TDI) effects were observed with 2 injectables on CYP1A, 5 injectables on CYP2A6, 5 injectables on CYP2B6, 6 injectables on CYP2C8, 1 injectable on CYP2D6 and 6 injectables on CYP3A. Collectively, the results demonstrate that potential herb-drug interactions (HDIs) can occur with the concomitant use of herb injectables and prescription drugs that are cleared by CYP450 enzymes, and further investigation is warrant for the clinical relevance of these interactions.

Article in Chinese | WPRIM | ID: wpr-257946


<p><b>OBJECTIVE</b>To investigate the therapeutic effect and safety of acupuncture at points of The Liver and Gallbladder Meridians for treatment of migraine.</p><p><b>METHODS</b>Multi-central, randomized and controlled trial was used and 253 cases of migraine were divided into an acupuncture group and a western medicine group. The acupuncture group was treated with acupuncture at points of The Liver and Gallbladder Channels with Taichong (LR 3), Yang-lingquan (GB 34), Fengchi (GB 20), Ququan (LR 8) selected as main points, and the western medicine group with oral administration of Flunarizine tablets for 4 therapeutic courses. The total therapeutic effects 3 and 6 months after the treatment, the scores of various symptoms of migraine before and after treatment, and the stability of therapeutic effect in one-year following-up survey were observed in the two groups.</p><p><b>RESULTS</b>After treatment, mean times and duration of the headache attack were significantly improved in the two groups (all P < 0.01) with the acupuncture group better than the western medicine group (P < 0.05). The total effective rates for stopping pain after treatment, 3 months and 6 months after treatment in the acupuncture group were 93.0%, 93.0% and 87.7%, respectively, which were better than 85.6%, 86.5% and 69.2% in the western medication group (all P < 0.01). One year later, the stability of the therapeutic effect in the acupuncture group was better than that in the western medicine group (P < 0.05); the adverse reaction and the compliance in the acupuncture group were significantly superior to those in the western medicine group.</p><p><b>CONCLUSION</b>Acupuncture at points of The Liver and Gallbladder Meridians for treatment of migraine is safe, effective, and with stable long-term therapeutic effect.</p>

Acupuncture Points , Acupuncture Therapy , Methods , Administration, Oral , Adolescent , Adult , Aged , Female , Flunarizine , Therapeutic Uses , Gallbladder , Pathology , Headache , Histamine H1 Antagonists , Therapeutic Uses , Humans , Liver , Pathology , Male , Meridians , Middle Aged , Migraine Disorders , Drug Therapy , Pathology , Therapeutics , Treatment Outcome , Young Adult
Article in Chinese | WPRIM | ID: wpr-260500


<p><b>OBJECTIVE</b>To evaluate the clinical therapeutic effect of acupuncture treatment of children cerebral palsy with gaining in wisdom and activating channels method.</p><p><b>METHODS</b>Sixty cases were randomly divided into a gaining in wisdom and activating channels group, a JIN's 3-needling group and a routine acupuncture group, 20 cases in each group. The gaining in wisdom and activating channels group was treated with point group of the head selected as main points combined with Dazhui (GV 14), Jinsuo (GV 8), Mingmen (GV 4), Yaoyangguan (GV 3), Hegu (LI 4), Neiguan (PC 6), Sanyinjiao (SP 6), etc., the JIN's 3-needling group was treated with Four-shen needling and Dazhui (GV 14), Shenzhu (GV 12), Fengfu (GV 16), etc. were selected as main acupoints in the routine acupuncture group. Comprehensive Function Evaluation for Disabled Children was used for assessment of comprehensive function of disabled children.</p><p><b>RESULTS</b>The total effective rate of 90.0% in both the gaining in wisdom and activating channels group and the JIN's 3-needling group, with no significant difference between the two groups (P > 0.05), were better than that of 60.0% in the routine acupuncture group (P < 0.05).</p><p><b>CONCLUSION</b>Acupuncture treatment with gaining in wisdom and activating channels method can significantly improve the comprehensive function of disabled children with more obvious therapeutic effects.</p>

Acupuncture Points , Acupuncture Therapy , Adolescent , Cerebral Palsy , Therapeutics , Child , Child, Preschool , Female , Humans , Male , Treatment Outcome