1.Research of in vitro Anti-tumor Effect of Hydroxychloroquine
Tao YANG ; Guoming LI ; Linlu XUE ; Bo HUANG ; Qi WANG ; Changsheng DENG ; Qin XU ; Jianping SONG
China Pharmacist 2016;19(3):417-419
Objective:To investigate and evaluate the anti-tumor activity of hydroxychloroquine ( HCQ) in vitro. Methods:CCK-8 assay was applied to detect the inhibitory effect of HCQ at different concentrations(4. 78, 9. 55, 19. 10, 38. 20,76. 40 μg?ml-1 ) on A549 cells, HepG2 cells, HT-29 cells, K562 cells, Hela cells and B16 cells. Absorbance was detected by a microplate reader, and then the inhibitory rate of the tumor cells and the IC50 was calculated. Results:Compared with those of the negative control group, the inhibitory rates of HCQ at different concentrations against the six tumor cells were all increased significantly in a dose-dependent manner (P<0. 01). The inhibitory rates of the tumor cells were all above 60% when the concentration reached 38. 20μg?ml-1. The IC50 was 26. 70(A549), 27. 47(HepG2), 5. 72(HT-29), 14. 03(K562), 20. 21(Hela) and 13. 62(B16) μg?ml-1, respectively. Conclusion:HCQ shows anti-tumor activity on several cancer cells in vitro. There may be a good application prospect for HCQ in the treatment of colorectal cancer, liver cancer, cervical cancer, melanoma and leukemia.
2.Molecular mechanism of damage and repair of mouse thymus lymphocytes induced by radiation.
Yufang CUI ; Hong YANG ; Shuxia WU ; Linlu GAO ; Yabing GAO ; Ruiyun PENG ; Xuemei CUI ; Chengqi XIONG ; Wenhua HU ; Dewen WANG
Chinese Medical Journal 2002;115(7):1070-1073
OBJECTIVETo investigate the role of apoptosis in radiation-induced mouse thymus lymphocyte damage and repair and provide the basis for understanding the molecular mechanism of radiation-induced lymphocyte damage and repair as well as the prevention and treatment of acute radiation sickness.
METHODSWe studied the dynamic changes of apoptosis of mouse thymus lymphocytes and the expression of bax and bcl-2 gene products after 2, 4, 6 and 8 Gy of whole body gamma-irradiation using in situ terminal labeling, DNA electrophoresis and immunohistochemical techniques.
RESULTSAt the early stage after irradiation, the percentage of apoptotic lymphocytes increased rapidly in accordance with the increasing of radiation doses, while the counts of the thymus and peripheral lymphocytes decreased sharply, showing an opposite change to lymphocyte apoptosis. After 6 Gy gamma-irradiation, typical morphological characteristics of thymus apoptotic lymphocytes in early, middle and late stages were found by transmission electron microscopy. The thymus lymphocytes displayed characteristic DNA ladders 4 hr and 8 hr after 2-6 Gy gamma-irradiation,using DNA gel electrophoresis techniques. Abnormal expression of bcl-2 and bax gene products were shown in irradiated lymphocytes.
CONCLUSIONSApoptosis plays an important role in the process of radiation-induced mouse thymus lymphocyte damage and repair. Bcl-2 and Bax proteins may regulate the process of lymphocyte apoptosis.
Animals ; Apoptosis ; radiation effects ; Dose-Response Relationship, Radiation ; Gamma Rays ; Lymphocytes ; physiology ; radiation effects ; Male ; Mice ; Proto-Oncogene Proteins ; analysis ; Proto-Oncogene Proteins c-bcl-2 ; analysis ; Thymus Gland ; pathology ; radiation effects ; Time Factors ; bcl-2-Associated X Protein
3.Incidence and prognosis of olfactory,gustatory and auditory dysfunctions related to infection of COVID-19 Omicron strain:A network-based survey
Linlu WANG ; Yihui WEN ; Jian LI ; Hua ZHONG ; Weiping WEN
Chinese Archives of Otolaryngology-Head and Neck Surgery 2024;31(1):26-30
OBJECTIVE To determine the incidence and prognosis of olfactory,gustatory and auditory dysfunctions related to the COVID-19 Omicron strain infection.METHODS A cross-sectional investigation was performed through online questionnaires.Data of patients with Omicron strain infection from December 24th,2022 to January 2nd,2023 were collected.The visual analogue scale(VAS)was used to evaluate the self-reported olfactory,gustatory and auditory functions of patients.RESULTS A total of 869 valid questionnaires were obtained.The incidence of otolaryngology-related symptoms associated with omicron strain infection was 96.8%.The incidence of olfactory,gustatory and auditory dysfunction was 44.4%,44.2%and 10.7%,respectively.There were statistically significant differences(P<0.001)in VAS scores for olfactory,gustatory,and auditory impairments between all surveyed individuals before and after infection,as well as in the corresponding VAS scores for those who experienced these impairments.The median duration of olfactory,gustatory and auditory dysfunction were 5,4 and 3 days,respectively.CONCLUSION The incidence of olfactory,gustatory,and auditory impairments is high after Omicron infection,with most cases experiencing rapid spontaneous improvement.For the long-term symptoms,the otolaryngology doctors are responsible for exploring and developing effective intervention measures.
4.Exploring the Mechanism of Action of Qizhu Kang'ai Formula (芪术抗癌方) for the Treatment of Colorectal Cancer based on Network Pharmacology and Experimental Validation
Ruolan SUN ; Yan LIANG ; Fan ZHAO ; Shijiao ZHU ; Linlu WAN ; Xu WANG ; Qihang YIN ; Gang YIN ; Decai TANG
Journal of Traditional Chinese Medicine 2024;65(4):404-413
ObjectiveTo explore the potential molecular mechanism of Qizhu Kang'ai Formula (芪术抗癌方, QZKAF) for the treatment of colorectal cancer (CRC). MethodsNetwork pharmacology was used to analyze the active ingredients and targets of QZKAF for CRC, and analyze the key targets of QZKAF for the treatment of CRC by gene function annotation (GO) and Kyoto Encyclopedia of Genomes (KEGG) pathway enrichment analysis. Molecular docking was applied to predict the binding activity of the core active ingredients to the key targets. A orthotopic transplantation tumor mice model of CRC was established to validate the key targets of QZKAF for CRC obtained from network pharmacology analysis. Forty-eight mice were randomly divided into the sham operation group, the model group, the 5-fluorouracil (5-Fu) group, and the QZKAF low-, medium-, and high-dose groups, with 8 mice in each group. Except for the sham operation group, the remaining groups underwent colon cancer orthotopic transplantation tumor modeling. The 5-Fu group was given 30 mg/kg of 5-Fu by intraperitoneal injection once every 3 days on the alternate day after modeling, while the QZKAF low-, medium-, and high-dose groups were given 2.925, 5.85, and 11.7 g/(kg·d) of QZKAF by gastric gavage, respectively, and the sham-operation group and the model group were gavaged with 0.1 ml/10 g of normal saline every day, all for 21 days. The in situ tumors mass and the number of liver metastases were compared between the groups. The pathological changes of colon tumor tissues were observed by HE staining, and the protein expression of protein tyrosine phosphatase nonreceptor type 1 (PTPN1), vinculin, integrin subunit αν, integrin subunit β3, and E-cadherin were detected in colon tumor tissues by Western blot. ResultsNetwork pharmacology screening yielded that the top six core active ingredients of QZKAF intervening in CRC were quercetin, kaempferol, apigenin, luteolin, baicalein and ursolic acid. There were 212 targets of action, and the ranked top three were prostaglandin endoperoxide synthase 1 (PTGS1), prostaglandin endoperoxide synthase 2 (PTGS2), and PTPN1, which may be the key targets of QZKAF in the treatment of CRC. These key targets were significantly enriched mainly in phosphatidylinositol 3-kinase/protein kinase B (PI3K-Akt) signaling pathway, focal adhesion and adhesion junction. Molecular docking results: except for PTGS1 with better binding activity to quercetin, kaempferol, and apigenin (binding energy ≥