BACKGROUND Bone is a major site of metastasis in nasopharyngeal carcinoma(NPC).Recently,nuclear factor kappa-beta ligand(RANKL)inhibitors have garnered attention for their ability to inhibit osteoclast formation and b...BACKGROUND Bone is a major site of metastasis in nasopharyngeal carcinoma(NPC).Recently,nuclear factor kappa-beta ligand(RANKL)inhibitors have garnered attention for their ability to inhibit osteoclast formation and bone resorption,as well as their potential to modulate immune functions and thereby enhance the efficacy of programmed cell death protein 1(PD-1)inhibitor therapy.CASE SUMMARY We present a case of a patient with NPC who developed sternal stalk metastasis and multiple bone metastases with soft tissue invasion following radical chemoradiotherapy and targeted therapy.Prior to chemotherapy,the patient experienced severe bone marrow suppression and opted out of further chemotherapy sessions.However,the patient received combination therapy,including RANKL inhibitors(denosumab)alongside PD-1,radiotherapy,and granulocyte-macrophage colonystimulating factor(PRaG)therapy(NCT05435768),and achieved 16 months of progression-free survival and more than 35 months of overall survival,without encountering any grade 2 or higher treatment-related adverse events.CONCLUSION Denosumab combined with PRaG therapy could be a new therapeutic approach for the second-line treatment in patients with bone metastases.展开更多
Objective： The aim of our study was to determine the underlying mechanism of miR-210 on regulation of the cell cycle in nasopharyngeal carcinoma cell line CNE-1, particularly through regulation of cyclin D1, under hy...Objective： The aim of our study was to determine the underlying mechanism of miR-210 on regulation of the cell cycle in nasopharyngeal carcinoma cell line CNE-1, particularly through regulation of cyclin D1, under hypoxic conditions. Methods： The CNE-1 cell line was induced with hypoxia, and the expression levels of endogenic miR-210 and cyclin D1 were detected by real-time PCR and Western blotting. Next, the luciferase assay was used to confirm that cyclin D1 is a target gene for miR-210. Cell cycle and cell proliferation were detected in CNE-1 cells that were cultured under hypoxic conditions with either overexpression or knockout of miR-210 using flow cytometry and MTT assay, respectively. Results： Hypoxia induced the expression of miR-210, resulting in reduced mRNA and protein levels of cyclin D1 and repression of cyclin D1 in CNE-1 cells. Further analysis indicated that miR-210 directly binded to the 3＇UTR of the cyclin D1 gene, thus regulated the expression of cyclin DI. The flow cytometry assay showed that, under hypoxic conditions, miR-210 blocked CNE-1 cells in the G1 phase, and miR-210 also inhibited the proliferation of CNE-1 cells. Conclusion： Under hypoxic conditions, miR-210 directly reduced the expression of cyclin D1, leading to CNE-1 cells blocked in G1 phase.展开更多
T cells modified with chimeric antigen receptor are an attractive strategy to treat Epstein-Barr virus（EBV） associated malignancies.The EBV latent membrane protein 1（LMP1） is a 66-KD integral membrane protein enco...T cells modified with chimeric antigen receptor are an attractive strategy to treat Epstein-Barr virus（EBV） associated malignancies.The EBV latent membrane protein 1（LMP1） is a 66-KD integral membrane protein encoded by EBV that consists of transmembrane-spanning loops.Previously,we have identified a functional signal chain variable fragment（scFv） that specifically recognizes LMP1 through phage library screening.Here,we constructed a LMP1 specific chimeric antigen receptor containing anti-LMP1 scFv,the CD28 signalling domain,and the CD3ζchain（HELA/CAR）.We tested its functional ability to target LMP1 positive nasopharyngeal carcinoma cells.HELA/CAR cells were efficiently generated using lentivirus vector encoding the LMP1-specific chimeric antigen receptor to infect activated human CD3＋ T cells.The HELA/CAR T cells displayed LMP1 specific cytolytic action and produced IFN-γ and IL-2 in response to nasopharyngeal carcinoma cells overexpressing LMP1.To demonstrate in vivo anti-tumor activity,we tested the HELA/CAR T cells in a xenograft model using an LMP1 overexpressing tumor.Intratumoral injection of anti-LMP1 HELA/CAR-T cells significantly reduced tumor growth in vivo.These results show that targeting LMP1 using HELA/CAR cells could represent an alternative therapeutic approach for patients with EBV-positive cancers.展开更多
Objective:To explore the role of proto-oncogene Pim-1 in the proliferation and migration of nasopharyngeal carcinoma(NPC) cells.Methods:Pim-1 expressions in NPC cell lines CNE1,CNE1-GL,CNE-2Z and C666-1 were examined ...Objective:To explore the role of proto-oncogene Pim-1 in the proliferation and migration of nasopharyngeal carcinoma(NPC) cells.Methods:Pim-1 expressions in NPC cell lines CNE1,CNE1-GL,CNE-2Z and C666-1 were examined by KT-PCR,western blotting and immunoflucesence,respectively.After CNE1,CNE1-GL and C666-1 cells were treated with different concentrations of Pim-1 special inhibitor,quercelagetin,the cell viability,colony formation rate and migration ability were analyzed.Results:Pim-1 expression was negative in well-differentiated CNE1 cells,whereas expressed weakly positive in poor-differentiated CNE-2Z cells and strongly positive in undifferentiated C666-1 cells.Interestingly,CNE1-GL cells that derived from CNE1 transfected with an Epstein Barr virus latent membrane protein-1 over-expression plasmid displayed stronger expression of Pim-1.Treatment of CNE1-GL and C666-1 cells with quercelagetin significantly decreased the cell viability,colony formation rate and migration ability but not the CNE1 cells.Conclusions:These findings suggest that Pim-1 overexpression contributes to NPC proliferation and migration,and targeting Pim-1 may be a potential treatment for anti-Pim-1-expressed NPCs.展开更多
Objective: To investigate the effects of Epstein- Barr virus (EBV) encoded latent membrane protein 1 (LMP1) expression on tumor cell differentiation in early-stage nasopharyngeal carcinoma (NPC). Methods: Thirty-one b...Objective: To investigate the effects of Epstein- Barr virus (EBV) encoded latent membrane protein 1 (LMP1) expression on tumor cell differentiation in early-stage nasopharyngeal carcinoma (NPC). Methods: Thirty-one biopsies of early-stage NPC were collected from the Cancer Center, Sun Yat-sen University. All 31 NPCs were of non-keratinizing carcinoma in histological type. The Epstein-Barr virus early RNAs (EBERs) were detected by use of DAKO PNA Probe (Y5200) and PNA ISH Detection Kit (K5201). The LMP1, a-catenin, b-catenin, g-catenin, high- molecular and low-molecular weight cytokeratins were detected by immunohistochemistry. Results: All 31 carcinoma biopsies studied showed a considerable number of EBERs-positive tumor cells, and 19 out of 31 cases (61.29%) expressed LMP1. The mean percentage of g-catenin expression in LMP1 positive group (53.25±34.12% ) was significantly lower than that (80.42±15.77%) in LMP1 negative group, (P<0.01). The g-catenin expression was positively correlated with the expression of low molecular weight cytokeratin (r=0.440, P<0.05). There were positive correlations for the expression of a-catenin, b-catenin and g-catenin in between. Conclusion: The LMP1 could down-regulate the expression of g-catenin and thus inhibit the tumor cell differentiation in early-stage NPC.展开更多
Objective:To study the LMP2A, AnnexinA2, Rad52 and Gli1 expression in nasopharyngeal carcinoma and their correlation with tumor malignancy.Methods:Nasopharyngeal cancer tissue confirmed by fibreoptic nasopharyngoscopi...Objective:To study the LMP2A, AnnexinA2, Rad52 and Gli1 expression in nasopharyngeal carcinoma and their correlation with tumor malignancy.Methods:Nasopharyngeal cancer tissue confirmed by fibreoptic nasopharyngoscopic biopsy and mild chronic rhinitis mucosa inflammation tissue in Renmin Hospital of Wuhan University between May 2014 and February 2017 were selected to extract the RNA, and then fluorescence quantitative PCR kits were used to determine the expression of LMP2A, AnnexinA2, Rad52, Gli1, epithelial-mesenchymal transition genes and cell cycle genes.Results: LMP2A, AnnexinA2, Rad52 and Gli1 mRNA expression in nasopharyngeal cancer lesions were significantly higher than those in rhinitis mucosa inflammation lesions, and the higher the clinical stage, the higher the LMP2A, AnnexinA2, Rad52 and Gli1 mRNA expression in nasopharyngeal cancer lesions;E-cadherin mRNA expression in nasopharyngeal cancer lesions was significantly lower than that in rhinitis mucosa inflammation lesions and negatively correlated with LMP2A and Gli1 while N-cadherin, Vimentin and ZEB2 mRNA expression were significantly higher than those in rhinitis mucosa inflammation lesions and positively correlated with LMP2A and Gli1;CyclinD1, CyclinE and PCNA mRNA expression in nasopharyngeal cancer lesions were significantly higher than those in rhinitis mucosa inflammation lesions and positively correlated with with AnnexinA2 and Rad52.Conclusion:The high expression of LMP2A, AnnexinA2, Rad52 and Gli1 in nasopharyngeal carcinoma can promote epithelial-mesenchymal transition and cell cycle process in cancer cells.展开更多
Objective To understand the effects of clock gene BMAL1 and HIF-1α(Hypoxia inducible factor-1α)on proliferation,migration and sensitivity to radiotherapy of nasopharyngeal carcinoma cells HONE1.At the same time,whet...Objective To understand the effects of clock gene BMAL1 and HIF-1α(Hypoxia inducible factor-1α)on proliferation,migration and sensitivity to radiotherapy of nasopharyngeal carcinoma cells HONE1.At the same time,whether the biological clock gene BMAL1 can affect the expression of HIF-1αprotein was investigated.It will lay the foundation for further study on the correlation between clock gene BMAL1 and HIF pathway.Methods BMAL1 gene overexpression and interference lentivirus and HIF-1αgene interference lentivirus were constructed respectively,and were transfected into nasopharyngeal carcinoma cells HONE1.Western blot was used to verify the establishment of overexpressed and knockdown BMAL1 cell lines and HIF-1αgene knockdown cell line,and to investigate the expression of HIF-1αprotein in overexpressed and knockdown BMAL1 cell lines.CCK-8 cell proliferation test and scratch test were used to analyze the proliferation and migration ability of cells.Cell apoptosis after radiotherapy was analyzed by flow cytometry.The effects of BMAL1 and HIF-1αon the sensitivity of HONE1 radiotherapy in nasopharyngeal carcinoma cells after X-ray irradiation at different doses(0Gy,2Gy,4Gy,6Gy)were detected by clone formation assay.Results The overexpression of BMAL1 gene and lentivirus interference were constructed to effectively up regulate and down regulate the expression of BMAL1 protein in nasopharyngeal carcinoma cells HONE1.Meanwhile,HIF-1αgene interference lentivirus was constructed to effectively down-regulate the expression of HIF-1αprotein in nasopharyngeal carcinoma cell line HONE1,and successfully screen out stable nasopharyngeal carcinoma cell lines.Western blot results showed that overexpression of BMAL1 gene could inhibit the expression of HIF-1αprotein in HONE1 of nasopharyngeal carcinoma cells,while knockdown of BMAL1 gene promoted the expression of HIF-1αprotein in HONE1 of nasopharyngeal carcinoma cells(P<0.05).CCK-8 cell proliferation and scratch test showed that overexpression of BMAL1 gene or knockdown of HIF-1αgene could inhibit the proliferation and migration of HONE1 cells(P<0.05).Flow cytometry results showed that after 8Gy irradiation for 72 h,the apoptosis rate of BMALl gene overexpression group was higher than that of the overexpression control group,similarly,the apoptosis rate of HIF-1αgene knockdown group was higher than that of the knockdown control group(P<0.05).After X-ray irradiation at different doses(0Gy,2Gy,4Gy,6Gy),clon-formation experiment showed that the clon-formation rate and cell survival fraction of BMALl overexpression group or HIF-1αknockdown group were lower than those of negative control group(P<0.05).Sigmaplot analysis showed that the D0,Dq and SF2 of the BMAL1 overexpression group or HIF-1αknockdown group were lower than those of the negative control group,and the radiosensitization ratios were 1.381 and 1.063,respectively.Conclusion Overexpression of BMAL1 gene can inhibit the proliferation and migration of nasopharyngeal carcinoma cell line HONE1,increase apoptosis after radiotherapy and improve radiosensitivity.Knock down HIF-1αGene can inhibit the proliferation and migration of nasopharyngeal carcinoma cell line HONE1,increase apoptosis after radiotherapy and improve radiosensitivity.In nasopharyngeal carcinoma cells HONE1,overexpression of BMAL1 gene can inhibit the expression of HIF-1αprotein while knockdown of BMAL1 gene can promote the expression of HIF-1αprotein.展开更多
基金Supported by The Suzhou Medical Center,No.Szlcyxzx202103The National Natural Science Foundation of China,No.82171828+15 种基金The Key R and D Plan of Jiangsu Province(Development of Social),No.BE2021652The Subject Construction Support Project of The Second Affiliated Hospital of Soochow University,No.XKTJHRC20210011The Wu Jieping Medical Foundation,No.320.6750.2021-01-12The Special Project of"Technological Innovation"Project of CNNC Medical Industry Co.Ltd,No.ZHYLTD2021001The Suzhou Science and Education Health Project,No.KJXW2021018Foundation of Chinese Society of Clinical Oncology,No.Y-pierrefabre202102-0113 and No.Y-XD202002/zb-0015The Beijing Bethune Charitable Foundation,No.STLKY0016The Research Projects of China Baoyuan Investment Co.Ltd,No.270004The Suzhou Gusu Health Talent Program,No.GSWS2022028The Open Project of State Key Laboratory of Radiation Medicine and Protection of Soochow University,No.GZN1202302The New Medical Technology Project of the Second Affiliated Hospital of Soochow University,No.23zl001The Multi-center Clinical Research Project for Major Diseases in Suzhou,No.DZXYJ202304The Postgraduate Research and Practice Innovation Program of Jiangsu Province,No.SJCX24_1814The Gusu Health Talent Research Fund,No.GSWS2022053The National Natural Science Foundation of China,No.82102824The Scientific Research Program for Young Talents of China National Nuclear Corporation。
文摘BACKGROUND Bone is a major site of metastasis in nasopharyngeal carcinoma(NPC).Recently,nuclear factor kappa-beta ligand(RANKL)inhibitors have garnered attention for their ability to inhibit osteoclast formation and bone resorption,as well as their potential to modulate immune functions and thereby enhance the efficacy of programmed cell death protein 1(PD-1)inhibitor therapy.CASE SUMMARY We present a case of a patient with NPC who developed sternal stalk metastasis and multiple bone metastases with soft tissue invasion following radical chemoradiotherapy and targeted therapy.Prior to chemotherapy,the patient experienced severe bone marrow suppression and opted out of further chemotherapy sessions.However,the patient received combination therapy,including RANKL inhibitors(denosumab)alongside PD-1,radiotherapy,and granulocyte-macrophage colonystimulating factor(PRaG)therapy(NCT05435768),and achieved 16 months of progression-free survival and more than 35 months of overall survival,without encountering any grade 2 or higher treatment-related adverse events.CONCLUSION Denosumab combined with PRaG therapy could be a new therapeutic approach for the second-line treatment in patients with bone metastases.
基金Supported by grants from the National Natural Science Foundation of China (No.31301117,No.JCYJ20120827150357364)
文摘Objective： The aim of our study was to determine the underlying mechanism of miR-210 on regulation of the cell cycle in nasopharyngeal carcinoma cell line CNE-1, particularly through regulation of cyclin D1, under hypoxic conditions. Methods： The CNE-1 cell line was induced with hypoxia, and the expression levels of endogenic miR-210 and cyclin D1 were detected by real-time PCR and Western blotting. Next, the luciferase assay was used to confirm that cyclin D1 is a target gene for miR-210. Cell cycle and cell proliferation were detected in CNE-1 cells that were cultured under hypoxic conditions with either overexpression or knockout of miR-210 using flow cytometry and MTT assay, respectively. Results： Hypoxia induced the expression of miR-210, resulting in reduced mRNA and protein levels of cyclin D1 and repression of cyclin D1 in CNE-1 cells. Further analysis indicated that miR-210 directly binded to the 3＇UTR of the cyclin D1 gene, thus regulated the expression of cyclin DI. The flow cytometry assay showed that, under hypoxic conditions, miR-210 blocked CNE-1 cells in the G1 phase, and miR-210 also inhibited the proliferation of CNE-1 cells. Conclusion： Under hypoxic conditions, miR-210 directly reduced the expression of cyclin D1, leading to CNE-1 cells blocked in G1 phase.
基金supported in part by grants from the Special Fund of Clinical Medicine in Jiangsu Province(BL2013038)the Graduate Student Innovation Fund(CXZZ12_0563)
文摘T cells modified with chimeric antigen receptor are an attractive strategy to treat Epstein-Barr virus（EBV） associated malignancies.The EBV latent membrane protein 1（LMP1） is a 66-KD integral membrane protein encoded by EBV that consists of transmembrane-spanning loops.Previously,we have identified a functional signal chain variable fragment（scFv） that specifically recognizes LMP1 through phage library screening.Here,we constructed a LMP1 specific chimeric antigen receptor containing anti-LMP1 scFv,the CD28 signalling domain,and the CD3ζchain（HELA/CAR）.We tested its functional ability to target LMP1 positive nasopharyngeal carcinoma cells.HELA/CAR cells were efficiently generated using lentivirus vector encoding the LMP1-specific chimeric antigen receptor to infect activated human CD3＋ T cells.The HELA/CAR T cells displayed LMP1 specific cytolytic action and produced IFN-γ and IL-2 in response to nasopharyngeal carcinoma cells overexpressing LMP1.To demonstrate in vivo anti-tumor activity,we tested the HELA/CAR T cells in a xenograft model using an LMP1 overexpressing tumor.Intratumoral injection of anti-LMP1 HELA/CAR-T cells significantly reduced tumor growth in vivo.These results show that targeting LMP1 using HELA/CAR cells could represent an alternative therapeutic approach for patients with EBV-positive cancers.
基金supported by grants from the Doctoral Program of Guangdong Medical College(B2010013)National Natural Science Foundation of China(81000073)Natural Foundation of Hainan Province of China 1811197, 310043,and 811201)
文摘Objective:To explore the role of proto-oncogene Pim-1 in the proliferation and migration of nasopharyngeal carcinoma(NPC) cells.Methods:Pim-1 expressions in NPC cell lines CNE1,CNE1-GL,CNE-2Z and C666-1 were examined by KT-PCR,western blotting and immunoflucesence,respectively.After CNE1,CNE1-GL and C666-1 cells were treated with different concentrations of Pim-1 special inhibitor,quercelagetin,the cell viability,colony formation rate and migration ability were analyzed.Results:Pim-1 expression was negative in well-differentiated CNE1 cells,whereas expressed weakly positive in poor-differentiated CNE-2Z cells and strongly positive in undifferentiated C666-1 cells.Interestingly,CNE1-GL cells that derived from CNE1 transfected with an Epstein Barr virus latent membrane protein-1 over-expression plasmid displayed stronger expression of Pim-1.Treatment of CNE1-GL and C666-1 cells with quercelagetin significantly decreased the cell viability,colony formation rate and migration ability but not the CNE1 cells.Conclusions:These findings suggest that Pim-1 overexpression contributes to NPC proliferation and migration,and targeting Pim-1 may be a potential treatment for anti-Pim-1-expressed NPCs.
基金This work was supported by a grant from The National Natural Science Foundation of China (No.39730900-II).
文摘Objective: To investigate the effects of Epstein- Barr virus (EBV) encoded latent membrane protein 1 (LMP1) expression on tumor cell differentiation in early-stage nasopharyngeal carcinoma (NPC). Methods: Thirty-one biopsies of early-stage NPC were collected from the Cancer Center, Sun Yat-sen University. All 31 NPCs were of non-keratinizing carcinoma in histological type. The Epstein-Barr virus early RNAs (EBERs) were detected by use of DAKO PNA Probe (Y5200) and PNA ISH Detection Kit (K5201). The LMP1, a-catenin, b-catenin, g-catenin, high- molecular and low-molecular weight cytokeratins were detected by immunohistochemistry. Results: All 31 carcinoma biopsies studied showed a considerable number of EBERs-positive tumor cells, and 19 out of 31 cases (61.29%) expressed LMP1. The mean percentage of g-catenin expression in LMP1 positive group (53.25±34.12% ) was significantly lower than that (80.42±15.77%) in LMP1 negative group, (P<0.01). The g-catenin expression was positively correlated with the expression of low molecular weight cytokeratin (r=0.440, P<0.05). There were positive correlations for the expression of a-catenin, b-catenin and g-catenin in between. Conclusion: The LMP1 could down-regulate the expression of g-catenin and thus inhibit the tumor cell differentiation in early-stage NPC.
基金Surface Project of Natural Science Foundation of China No:81372407.
文摘Objective:To study the LMP2A, AnnexinA2, Rad52 and Gli1 expression in nasopharyngeal carcinoma and their correlation with tumor malignancy.Methods:Nasopharyngeal cancer tissue confirmed by fibreoptic nasopharyngoscopic biopsy and mild chronic rhinitis mucosa inflammation tissue in Renmin Hospital of Wuhan University between May 2014 and February 2017 were selected to extract the RNA, and then fluorescence quantitative PCR kits were used to determine the expression of LMP2A, AnnexinA2, Rad52, Gli1, epithelial-mesenchymal transition genes and cell cycle genes.Results: LMP2A, AnnexinA2, Rad52 and Gli1 mRNA expression in nasopharyngeal cancer lesions were significantly higher than those in rhinitis mucosa inflammation lesions, and the higher the clinical stage, the higher the LMP2A, AnnexinA2, Rad52 and Gli1 mRNA expression in nasopharyngeal cancer lesions;E-cadherin mRNA expression in nasopharyngeal cancer lesions was significantly lower than that in rhinitis mucosa inflammation lesions and negatively correlated with LMP2A and Gli1 while N-cadherin, Vimentin and ZEB2 mRNA expression were significantly higher than those in rhinitis mucosa inflammation lesions and positively correlated with LMP2A and Gli1;CyclinD1, CyclinE and PCNA mRNA expression in nasopharyngeal cancer lesions were significantly higher than those in rhinitis mucosa inflammation lesions and positively correlated with with AnnexinA2 and Rad52.Conclusion:The high expression of LMP2A, AnnexinA2, Rad52 and Gli1 in nasopharyngeal carcinoma can promote epithelial-mesenchymal transition and cell cycle process in cancer cells.
基金supported in part by grants from the National Natural Science Foundation of China under grant number 82060556,81560437the Department of Science and Technology,Guizhou Province,under grant number[2018]2755+3 种基金the Ordinary Colleges and Universities Youth Science and Technology Talent Growth Project,Guizhou Province,under grant number[2021]187The Health Commission Science and Technology Fund,Guizhou Provincial under grant number gzwkj2021-050Guizhou Medical University 2021 National Foundation Cultivation Project[20NSP041]the Hospital-level Science and Technology Project of Guizhou Cancer Hospital under grant number YJ2019-33.
文摘Objective To understand the effects of clock gene BMAL1 and HIF-1α(Hypoxia inducible factor-1α)on proliferation,migration and sensitivity to radiotherapy of nasopharyngeal carcinoma cells HONE1.At the same time,whether the biological clock gene BMAL1 can affect the expression of HIF-1αprotein was investigated.It will lay the foundation for further study on the correlation between clock gene BMAL1 and HIF pathway.Methods BMAL1 gene overexpression and interference lentivirus and HIF-1αgene interference lentivirus were constructed respectively,and were transfected into nasopharyngeal carcinoma cells HONE1.Western blot was used to verify the establishment of overexpressed and knockdown BMAL1 cell lines and HIF-1αgene knockdown cell line,and to investigate the expression of HIF-1αprotein in overexpressed and knockdown BMAL1 cell lines.CCK-8 cell proliferation test and scratch test were used to analyze the proliferation and migration ability of cells.Cell apoptosis after radiotherapy was analyzed by flow cytometry.The effects of BMAL1 and HIF-1αon the sensitivity of HONE1 radiotherapy in nasopharyngeal carcinoma cells after X-ray irradiation at different doses(0Gy,2Gy,4Gy,6Gy)were detected by clone formation assay.Results The overexpression of BMAL1 gene and lentivirus interference were constructed to effectively up regulate and down regulate the expression of BMAL1 protein in nasopharyngeal carcinoma cells HONE1.Meanwhile,HIF-1αgene interference lentivirus was constructed to effectively down-regulate the expression of HIF-1αprotein in nasopharyngeal carcinoma cell line HONE1,and successfully screen out stable nasopharyngeal carcinoma cell lines.Western blot results showed that overexpression of BMAL1 gene could inhibit the expression of HIF-1αprotein in HONE1 of nasopharyngeal carcinoma cells,while knockdown of BMAL1 gene promoted the expression of HIF-1αprotein in HONE1 of nasopharyngeal carcinoma cells(P<0.05).CCK-8 cell proliferation and scratch test showed that overexpression of BMAL1 gene or knockdown of HIF-1αgene could inhibit the proliferation and migration of HONE1 cells(P<0.05).Flow cytometry results showed that after 8Gy irradiation for 72 h,the apoptosis rate of BMALl gene overexpression group was higher than that of the overexpression control group,similarly,the apoptosis rate of HIF-1αgene knockdown group was higher than that of the knockdown control group(P<0.05).After X-ray irradiation at different doses(0Gy,2Gy,4Gy,6Gy),clon-formation experiment showed that the clon-formation rate and cell survival fraction of BMALl overexpression group or HIF-1αknockdown group were lower than those of negative control group(P<0.05).Sigmaplot analysis showed that the D0,Dq and SF2 of the BMAL1 overexpression group or HIF-1αknockdown group were lower than those of the negative control group,and the radiosensitization ratios were 1.381 and 1.063,respectively.Conclusion Overexpression of BMAL1 gene can inhibit the proliferation and migration of nasopharyngeal carcinoma cell line HONE1,increase apoptosis after radiotherapy and improve radiosensitivity.Knock down HIF-1αGene can inhibit the proliferation and migration of nasopharyngeal carcinoma cell line HONE1,increase apoptosis after radiotherapy and improve radiosensitivity.In nasopharyngeal carcinoma cells HONE1,overexpression of BMAL1 gene can inhibit the expression of HIF-1αprotein while knockdown of BMAL1 gene can promote the expression of HIF-1αprotein.
