1.PX-478 enhances the effect of lung cancer radiotherapy by regulating HIF-1α-mediated glycolysis
Gengqiang YANG ; Yangyang LI ; Qiyang LI ; Shangzu ZHANG ; Yue YANG ; Ting ZHOU ; Liying ZHANG
Chinese Journal of Clinical Pharmacology and Therapeutics 2025;30(7):935-941
AIM:To study the efficacy and molecu-lar mechanism of PX-478 in enhancing radiotherapy effect of lung cancer.METHODS:H460,A549 cells were divided into blank group,radiation group and radiation combined PX-478 group.In addition to the blank group,the radiation group and the PX-478 group were given 2Gy X-ray irradiation to estab-lish the radiation model,and the radiation com-bined with the PX-478 group was given 20 μmol/L PX-478 intervention after modeling,and cultured for 24 h.Inverted microscope was used to observe cell growth and cell number,CCK-8 method was used to detect cell viability,cloning was used to ob-serve cell proliferation,flow cytometry was used to detect cell apoptosis,and Western blot was used to detect HIF-1α,GLUT1,HK2,PFK1,PKM2,LDHA pro-tein expression.RESULTS:Compared with blank group,the number of H460,A549 cells in radiation group decreased,cell viability and proliferation abil-ity decreased,cell apoptosis rate increased,HIF-1α,GLUT1,HK2,PFK1,PKM2,LDHA protein expression increased(P<0.01).Compared with the radiation group,the number of H460,A549 cells in the radia-tion combined PX-478 group was significantly de-creased,the cell viability and proliferation ability were significantly weakened,the apoptosis rate was significantly increased,and the protein expres-sions of HIF-1α,GLUT1,HK2,PFK1,PKM2 and LDHA were significantly decreased(P<0.01).CONCLU-SION:PX-478 can regulate the HIF-1α-mediated gly-colysis in A549,H460 cells after radiation,regulate the energy metabolism,increase the apoptosis of tumor cells,and improve the effect of radiotherapy.
2.PX-478 enhances the effect of lung cancer radiotherapy by regulating HIF-1α-mediated glycolysis
Gengqiang YANG ; Yangyang LI ; Qiyang LI ; Shangzu ZHANG ; Yue YANG ; Ting ZHOU ; Liying ZHANG
Chinese Journal of Clinical Pharmacology and Therapeutics 2025;30(7):935-941
AIM:To study the efficacy and molecu-lar mechanism of PX-478 in enhancing radiotherapy effect of lung cancer.METHODS:H460,A549 cells were divided into blank group,radiation group and radiation combined PX-478 group.In addition to the blank group,the radiation group and the PX-478 group were given 2Gy X-ray irradiation to estab-lish the radiation model,and the radiation com-bined with the PX-478 group was given 20 μmol/L PX-478 intervention after modeling,and cultured for 24 h.Inverted microscope was used to observe cell growth and cell number,CCK-8 method was used to detect cell viability,cloning was used to ob-serve cell proliferation,flow cytometry was used to detect cell apoptosis,and Western blot was used to detect HIF-1α,GLUT1,HK2,PFK1,PKM2,LDHA pro-tein expression.RESULTS:Compared with blank group,the number of H460,A549 cells in radiation group decreased,cell viability and proliferation abil-ity decreased,cell apoptosis rate increased,HIF-1α,GLUT1,HK2,PFK1,PKM2,LDHA protein expression increased(P<0.01).Compared with the radiation group,the number of H460,A549 cells in the radia-tion combined PX-478 group was significantly de-creased,the cell viability and proliferation ability were significantly weakened,the apoptosis rate was significantly increased,and the protein expres-sions of HIF-1α,GLUT1,HK2,PFK1,PKM2 and LDHA were significantly decreased(P<0.01).CONCLU-SION:PX-478 can regulate the HIF-1α-mediated gly-colysis in A549,H460 cells after radiation,regulate the energy metabolism,increase the apoptosis of tumor cells,and improve the effect of radiotherapy.
3.Multidimensional screening of Astragalus membranaceus small molecules to mitigate carbon ion radiation-induced bystander effects
Zhang LIYING ; Zhang YIMING ; Li YANGYANG ; Li QIYANG ; Zhang SHANGZU ; Miao ZHIMING ; He JINPENG ; Zhou TING ; Yang GENGQIANG ; Wang XIN ; Wang JUFANG ; Liu YONGQI
Journal of Pharmaceutical Analysis 2024;14(10):1531-1534
Existing studies have shown that Astragalus membranaceus(AM)and its active ingredients astragalus polysaccharides,oninon,and astragalus methyl glycosides can attenuate X-ray radiation-induced injury.However,there are no studies on how isoliquiritigenin(ISL)attenuate the bystander effect of bone marrow mesenchymal stem cells(BMSCs)induced by carbon ion radiation therapy for lung cancer.This study aimed to investigate the AM-derived small molecule ISL to enhance radiotherapy sensitivity by attenuating the carbon ion radiation-induced bystander effect(RIBE)in BMSCs to elucidate its mecha-nism of action.In this study,we established a C57BL/6 mouse lung cancer transplantation tumor model in vivo and a co-culture model of A549 cells and BMSCs in vitro,and the models were successfully treated with carbon ions.In further work,we used flow cytometry,immunofluorescence,Western blot,enzyme-linked immunosorbent assay(ELISA),inhibitor,short hairpin RNA(shRNA),Cell Counting Kit-8(CCK-8),and other methods to illustrate the mechanism.In the next experiments,we found that ISL combined with carbon ion radiotherapy had a significant anti-tumor effect and protected BMSCs from radiation damage.The aim of this study was to investigate the potential of ISL in enhancing the sensitivity of lung cancer cells to radiotherapy and attenuating RIBE in both in vitro and in vivo settings.Traditional Chinese medicine combined with radiation therapy is a promising and innovative treatment for non-small cell lung cancer.These results establish a theoretical foundation for further clinical development of ISL as a potential radiosensitizer option.
4.Expression and clinical predictive value of CHST6 in glioma patients
Beichuan ZHAO ; Ruoheng XUAN ; Guitao YANG ; Gengqiang LING ; Zhibo XIA
Chinese Journal of Nervous and Mental Diseases 2023;49(9):519-526
Objective To explore the relationship between carbohydrate sulfotransferase 6(CHST6)expression level and prognosis in glioma patients and construct prognosis model by using bioinformatics method.Methods To analyze the difference of CHST6 expression in glioma.The median CHST6 expression was divided into high and low expression groups.The prognostic differences between the groups were analyzed.The expression level of CHST6 and different clinical features were analyzed by Cox regression,and the prediction and improvement model was established,and the validity improvement was compared with the control model.Results A total of 1204 medical records were included in TCGA and CGGA databases.CHST6 was significantly up-regulated in glioma samples(TCGA vs.GTEx,Z= 2.457,P<0.001;CGGA vs.GTEx,Z=4.800,P<0.001),and was an independent prognostic factor for glioma together with age,WHO grade,IDH mutation status,and 1p19q co-deletion(Cox analysis β=0.02,SE=0.01,HR=1.02,95%CI:1.01~1.04,P=0.01;C-Index 0.885,95%CI:0.862~0.908),has higher predictive validity than the control model(Improved model vs.Control model:TCGA d=0.036±0.004,SE=0.002,P=0.007;CGGA d=0.087±0.004,SE=0.002,P=0.001).Conclusion The high expression of CHST6 may be a predictor of poor prognosis and abnormal immune function in glioma patients.

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