1.EIF5A1 Promotes Proliferation,Migration and Invasion of Intrahepatic Cholangiocarcinoma Cells Through Wnt Signaling Pathway
Shaohua YANG ; Yongping XU ; Zhuoyu ZHAO ; Xingbao FANG ; Zhenxing RUAN
Journal of Kunming Medical University 2025;46(7):46-53
Objective To investigate the expression of EIF5A1 in intrahepatic cholangiocarcinoma cell lines and human hepatobiliary duct epithelia,and its effect on the proliferation,migration and invasion ability and Wnt/β-Catenin signaling pathway in HUCCT1 cells.Methods Western blot was used to detect the basal expression level of EIF5A1 in intrahepatic cholangiocarcinoma cell lines and human intrahepatic cholangiocarcinoma epithelial cells.Transient transfection of siRNA was used to silence the expression of EIF5A1 in intrahepatic cholangiocarcinoma cell HUCCT1.The experimental groups were divided into blank control group(Con),siRNA1 group,and siRNA2 group.The most effective siRNA was screened by Western blot.The effects of EIF5A1 silencing on the proliferation,migration and invasion ability of HUCCT1 cells were detected by CCK-8,EdU cell proliferation assay and Transwell assay.The effect of EIF5A1 silencing on the Wnt/β-Catenin signaling pathway in HUCCT1 cells was detected by Western blot.Results The results of CCK-8 and EdU cell proliferation experiments showed that the proliferation ability of HUCCT1 cells decreased after EIF5A1 silencing(P<0.05),and Transwell migration and invasion experiments showed that the migration and invasion ability of Hucct1 cells decreased after EIF5A1 silencing(P<0.05).Western blot analysis revealed decreased expression of β-Catenin,Cyclin D1,MMP-2 and Survivin in Wnt/β-Catenin signaling pathway after EIF5A1 silencing(P<0.05).Conclusion EIF5A1 may promote the proliferation,migration and invasion of intrahepatic bile duct cancer cells through Wnt/β-Catenin signaling pathway.
2.Sex disparity of lung cancer risk in non-smokers: a multicenter population-based prospective study based on China National Lung Cancer Screening Program
Zheng WU ; Fengwei TAN ; Zhuoyu YANG ; Fei WANG ; Wei CAO ; Chao QIN ; Xuesi DONG ; Yadi ZHENG ; Zilin LUO ; Liang ZHAO ; Yiwen YU ; Yongjie XU ; Jiansong REN ; Jufang SHI ; Hongda CHEN ; Jiang LI ; Wei TANG ; Sipeng SHEN ; Ning WU ; Wanqing CHEN ; Ni LI ; Jie HE
Chinese Medical Journal 2022;135(11):1331-1339
Background::Non-smokers account for a large proportion of lung cancer patients, especially in Asia, but the attention paid to them is limited compared with smokers. In non-smokers, males display a risk for lung cancer incidence distinct from the females—even after excluding the influence of smoking; but the knowledge regarding the factors causing the difference is sparse. Based on a large multicenter prospective cancer screening cohort in China, we aimed to elucidate the interpretable sex differences caused by known factors and provide clues for primary and secondary prevention.Methods::Risk factors including demographic characteristics, lifestyle factors, family history of cancer, and baseline comorbidity were obtained from 796,283 Chinese non-smoking participants by the baseline risk assessment completed in 2013 to 2018. Cox regression analysis was performed to assess the sex difference in the risk of lung cancer, and the hazard ratios (HRs) that were adjusted for different known factors were calculated and compared to determine the proportion of excess risk and to explain the existing risk factors.Results::With a median follow-up of 4.80 years, 3351 subjects who were diagnosed with lung cancer were selected in the analysis. The lung cancer risk of males was significantly higher than that of females; the HRs in all male non-smokers were 1.29 (95% confidence interval [CI]: 1.20-1.38) after adjusting for the age and 1.38 (95% CI: 1.28-1.50) after adjusting for all factors, which suggested that known factors could not explain the sex difference in the risk of lung cancer in non-smokers. Known factors were 7% (|1.29-1.38|/1.29) more harmful in women than in men. For adenocarcinoma, women showed excess risk higher than men, contrary to squamous cell carcinoma; after adjusting for all factors, 47% ([1.30-1.16]/[1.30-1]) and 4% ([7.02-6.75]/[7.02-1])) of the excess risk was explainable in adenocarcinoma and squamous cell carcinoma. The main causes of gender differences in lung cancer risk were lifestyle factors, baseline comorbidity, and family history.Conclusions::Significant gender differences in the risk of lung cancer were discovered in China non-smokers. Existing risk factors did not explain the excess lung cancer risk of all non-smoking men, and the internal causes for the excess risk still need to be explored; most known risk factors were more harmful to non-smoking women; further exploring the causes of the sex difference would help to improve the prevention and screening programs and protect the non-smoking males from lung cancers.
3.Analysis of low-dose computed tomography compliance and related factors among high-risk population of lung cancer in three provinces participating in the cancer screening program in urban China
Yan WEN ; Lianzheng YU ; Lingbin DU ; Donghua WEI ; Yunyong LIU ; Zhuoyu YANG ; Yadi ZHENG ; Zheng WU ; Xinyang YU ; Liang ZHAO ; Yiwen YU ; Hongda CHEN ; Jiansong REN ; Chao QIN ; Yongjie XU ; Wei CAO ; Fei WANG ; Jiang LI ; Fengwei TAN ; Min DAI ; Wanqing CHEN ; Ni LI ; Jie HE
Chinese Journal of Preventive Medicine 2021;55(5):633-639
Objective:To analyze the compliance and related factors of low-dose computed tomography (LDCT) screening among the high-risk population of lung cancer in three provinces participating in the cancer early diagnosis and early treatment program in urban areas of China.Methods:From October 2017 to October 2018, 17 983 people aged between 40 and 74 years old at high risk of lung cancer were recruited from Zhejiang, Anhui and Liaoning provinces. The basic demographic characteristics, living habits, history of the disease and family history of cancer were collected by using a cancer risk assessment questionnaire, and the data of participants examined by LDCT were obtained from the hospitals participating in the program. The screening compliance was quantified by the screening participation rate, and it was calculated as the proportion of participants completing LDCT scan among high-risk population. The related factors of LDCT screening compliance were analyzed by using a multivariate logistic regression model.Results:The age of 17 983 participants was (56.52±8.22) years old. Males accounted for 51.9% (N=9 332), and 69.5% (N=12 495) had ever smoked, including former smokers and current smokers. A total of 6 269 participants were screened by LDCT, and the screening participation rate was 34.86%. The results of multivariate logistic regression analysis showed that the age group of 50 to 69 years old, female, passive smokers, alcohol consumption, family history of lung cancer and history of chronic respiratory diseases were more likely to be screened by LDCT, while the compliance of LDCT screening in current smokers was low.Conclusions:The LDCT screening compliance of the high-risk population of lung cancer in urban areas of China still needs to be improved. Age, sex, smoking, drinking, family history of lung cancer and history of chronic respiratory disease are associated with screening compliance.
4.Analysis of low-dose computed tomography compliance and related factors among high-risk population of lung cancer in three provinces participating in the cancer screening program in urban China
Yan WEN ; Lianzheng YU ; Lingbin DU ; Donghua WEI ; Yunyong LIU ; Zhuoyu YANG ; Yadi ZHENG ; Zheng WU ; Xinyang YU ; Liang ZHAO ; Yiwen YU ; Hongda CHEN ; Jiansong REN ; Chao QIN ; Yongjie XU ; Wei CAO ; Fei WANG ; Jiang LI ; Fengwei TAN ; Min DAI ; Wanqing CHEN ; Ni LI ; Jie HE
Chinese Journal of Preventive Medicine 2021;55(5):633-639
Objective:To analyze the compliance and related factors of low-dose computed tomography (LDCT) screening among the high-risk population of lung cancer in three provinces participating in the cancer early diagnosis and early treatment program in urban areas of China.Methods:From October 2017 to October 2018, 17 983 people aged between 40 and 74 years old at high risk of lung cancer were recruited from Zhejiang, Anhui and Liaoning provinces. The basic demographic characteristics, living habits, history of the disease and family history of cancer were collected by using a cancer risk assessment questionnaire, and the data of participants examined by LDCT were obtained from the hospitals participating in the program. The screening compliance was quantified by the screening participation rate, and it was calculated as the proportion of participants completing LDCT scan among high-risk population. The related factors of LDCT screening compliance were analyzed by using a multivariate logistic regression model.Results:The age of 17 983 participants was (56.52±8.22) years old. Males accounted for 51.9% (N=9 332), and 69.5% (N=12 495) had ever smoked, including former smokers and current smokers. A total of 6 269 participants were screened by LDCT, and the screening participation rate was 34.86%. The results of multivariate logistic regression analysis showed that the age group of 50 to 69 years old, female, passive smokers, alcohol consumption, family history of lung cancer and history of chronic respiratory diseases were more likely to be screened by LDCT, while the compliance of LDCT screening in current smokers was low.Conclusions:The LDCT screening compliance of the high-risk population of lung cancer in urban areas of China still needs to be improved. Age, sex, smoking, drinking, family history of lung cancer and history of chronic respiratory disease are associated with screening compliance.
5. Therapeutic and immunomodulatory effects of human umbilical cord-derived mesenchymal stem cells on adjuvant arthritis in rats
Run CHENG ; Wenxi DING ; Zhuoyu CHENG ; Jichen HE ; Yingjie ZHAO ; Shangxue YAN ; Wei WEI
Chinese Journal of Primary Medicine and Pharmacy 2019;26(19):2327-2331
Objective:
To investigate the therapeutic and immunomodulatory effects of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) on adjuvant arthritis(AA) rats.
Methods:
Twenty-four male Sprague-Dawley(SD) rats were established with AA by complete Freund's adjuvant method.They were randomly divided into model group and hUC-MSCs group (2×106 cells/mL, 5×106 cells/mL, tail vein injection), and the Yisaipu group (2.8mg/kg, subcutaneous injection), 6 rats in each group.Another 6 male SD rats were used as the control group.After the model was established, the body weight and paw volume were recorded weekly, the whole body score and the arthritis index score were calculated, and the joint swelling number was calculated.The animals were sacrificed after d35, the weight of thymus and spleen were weighed, and the corresponding index was calculated, the histopathological changes of the ankle joint were observed by HE staining.The percentages of CD4+ CD44+ T cell and CD4+ CD62L+ T cell were detected by flow cytometry.The levels of TNF-α, IL-1β in the serum of AA rats were detected by ELISA.
Results:
hUC-MSCs relieved paw volume, the whole body score and arthritis index score, and the joint swelling number in AA rats (
6.Effect of low concentrations of p,p′- dichlorodipheny ltrichloroethane on proliferation and apoptosis of coIorectal adenocarcinoma SW620 cells
Jianxin LLU ; Junyu ZHAO ; Xiaoting JLN ; Zhuoyu LL ; Li SONG
Chinese Journal of Pharmacology and Toxicology 2015;(2):227-233
OBJECTIVE To investigate the effect and mechanism of low concentrations of p,p′-dichlorodiphenyltrichloroethane (p,p′-DDT) on colorectal adenocarcinoma SW620 cell proliferation and apoptosis. METHODS SW620 cells were exposed to low concentrations of p, p′-DDT ranging from 1×10-12 to 1×10-6 mol.L-1 for 48 and 96 h. MTT assay was employed to examine the effect of p,p′-DDT on SW620 cell viability. Different cell stages of cycle and apoptosis rate were determined by flow cytometry after SW620 cells were exposed to 1×10-10 , 1×10-9 and 1×10-8 mol.L-1 for 96 h. Western blotting was used to determine the protein expression of Wnt/ β-catenin signaling components 〔β-catenin, phospho-β-catenin and phospho-glycogen synthase kinase ( GSK) 3β〕, their downstream target proteins ( c-Myc and cyclin D1)and apoptosis related proteins (Bcl-2, Bax, procaspase 8 and procaspase 3). RESULTS The viability of colorectal adenocarcinoma SW620 cells was significantly increased after exposure to low concentrations of p,p′-DDT ranging from 1×10-12 to 1×10-7 mol.L-1 for 96 h. p,p′-DDT 1×10-10 , 1×10-9 and 1×10-8 mol.L-1 exposure led to a decreased percentage of SW620 cells in G1 stage(P<0.01) along with an increased percentage of cells in S stage(P<0.01). Meanwhile, the apoptosis rate was signifi-cantly decreased compared with control group ( P < 0. 01). Exposure to p, p′-DDT from 1 × 10-10 to 1×10-8 mol.L-1 induced upregulation of phospho-GSK3β ( Ser9), β-catenin, c-Myc and cyclin D1 in SW620 cells( P <0.01). Moreover, apoptosis related proteins Bcl-2, procaspase 8 and procaspase 3 were unregulated(P<0.01), and Bax level and caspase 3 activity were decreased in p,p′-DDT-stimulated cells(P < 0.01). CONCLUSION Low concentrations of p, p′-DDT exposure activates Wnt/ β-catenin signaling and affects apoptosis-related proteins, which may be involved in p,p′-DDT-induced cell prolifer-ation as well as suppression of cell apoptosis in SW620 cells.
7.Effects of trypsin inhibitors on Wnt signaling pathway and cellular apoptosis
Yarui ZHAO ; Zongwei LI ; Xinghua WANG ; Zhuoyu LI
Cancer Research and Clinic 2011;23(10):718-720
The trypsin inhibitor is a kind of substance that can inhibit trypsin activity.It shares extensive physiological roles.The trypsin inhibitor not only inhibits the activities of many enzymes,but also has significant anti-cancer effects by suppressing cell invasion and promoting cell apoptosis.Wnt signaling pathway involves in the regulation of cell growth,proliferation and apoptosis.It also plays an important role in tumor development.This review focuses on the impacts of trypsin inhibitors on Wnt signaling pathway and tumor cell apoptosis.

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