1.THE EFFECT OF ?-ELEMECE ON REVERSAL MULTIDRUG RESISTANCE AND THE EXPRESSION OF P-GLYCOPROTEIN IN K562/ADM
Lihong HAO ; Jinyao ZHAO ; Chuanzhou GAO ; Yanfang DING ; Peiman YANG
Acta Anatomica Sinica 1953;0(01):-
Objective To explore the effect of ?-elemece on the reverse of drug resistance and the expression of P-glycoprotein(P-gp) in MDR K562/ADM cells. Methods MTT method was used to detect the sensitivity of cell and its reverse of drug resistance.Immunohistochemistry and immunoelectron microscopy were for observing the expression of P-gp.It's quantitative analysis was determined by flow cytometry.All experimental data were dealt with by SPSS(10.0 production pacility) soft ware. Results 1.Non-cytotoxic dose of ?-elemece(4.0?mg/L) could obviously decrease the IC-(50) value of K562/ADM cells to ADM.The reversing fold was 2.18;2.The level of P-gp expression was higher in K562/ADM cells than that in its parent K562 cells.Our studies also showed that the distribution of P-gp was on membrane of K562/ADM cells;3.Non-cytotoxic dose of ?-elemece(4.0?mg/L) could remarkably decrease the P-gp expression in MDR K562/ADM cells.Conclusion\ ?-elemece could evidently reverse drug resistance of K562/ADM to ADM.Decreasing the P-gp expression in drug resistance cell is one of the main mechanism of reversion.
2.Clinical Observation of Kangfuxin Liquid in the Treatment of Radioactive Dermatitis of Nasopharyngeal Carcinoma Patients
Zhiping FENG ; Yuanhua SONG ; Zhiyong DENG ; Yaoxiong XIA ; Chao LIU ; Fukun CHEN ; Chuanzhou YANG
China Pharmacy 2018;29(10):1392-1395
OBJECTIVE:To observe clinical efficacy and safety of Kangfuxin liquid in the treatment of radioactive dermatitis of nasopharyngeal carcinoma patients. METHODS:A total of 73 nasopharyngeal carcinoma patients with radioactive dermatitis in the Third Affiliated Hospital of Kunming Medical University during Feb. 2016 to Feb. 2017 were divided into control group (36 cases) and observation group (37 cases) according to random number table. Both groups received routine treatment as Methylrosanilinium chloride solution,Compound cod liver oil and zinc oxide ointment for external use. Observation group was additionally given gauze soaked with Kangfuxin liquid on affected area,3 times a day on the basis of routine treatment. Both groups were treated for 4 weeks. Clinical efficacies of 2 groups were compared,and RTOG classification and dermatitis area were compared before and after treatment. The occurrence of ADR was recorded. RESULTS:There was statistical significance in the total response rate between observation group (94.6%) and control group (97.2%)(P<0.05). Before and after treatment,there were no RTOG Ⅳ patients in 2 groups. Before treatment,there was no statistical significance in the proportion of RTOG 0-Ⅲpatients or dermatitis area between 2 groups (P>0.05). After treatment,RTOG classification of observation group was improved significantly, the proportion of grade 0 patients was significantly higher than control group, that of gradeⅠpatients was significantly lower than control group,with statistical significance(P<0.05). There was no statistical significance in the proportion of RTOG 0-Ⅲpatients of control group before and after treatment(P>0.05). Two,four weeks after treatment,dermatitis areas of 2 groups were decreased significantly;dermatitis area 4 weeks after treatment was significantly smaller than 2 weeks after treatment;observation group was significantly smaller than control group,with statistical significance(P<0.05). No obvious ADR was found in 2 groups during treatment. CONCLUSIONS:Additional use of Kangfuxin liquid in the treatment of radioactive dermatitis of nasopharyngeal carcinoma patients can effectively relieve symptoms and reduce dermatitis area with good safety.
3.BRD4 inhibitor specifically inhibits the development of wild-type Kras differentiated thyroid carcinoma by regulating BRD4/miR-106b-5p/P21 axis
Zhiping FENG ; Chuanzhou YANG ; Ting CHEN ; Jialun ZHU ; Chao LIU ; Juan LYU ; Jianmei LU ; Zhiyong DENG
Journal of International Oncology 2021;48(8):463-472
Objective:To explore the influence of bromodomain-containing protein 4 (BRD4) inhibitor on wild-type Kras differentiated thyroid carcinoma (DTC) and its mechanism.Methods:The DTC cell line Kras WT TPC-1 was selected and the mutant Kras G12D TPC-1 cells were constructed. CCK-8 assay was used to detect the effect of BRD4 inhibitor JQ-1 on the proliferation activity of Kras WT TPC-1 cells. Kras WT TPC-1 cells were treated with 0.2 μmol/L JQ-1 (JQ-1 group), and a negative control group (NC group) was set. Transwell invasion assay and flow cytometry were used to detect the effect of JQ-1 on the invasion and apoptosis of Kras WT TPC-1 cells. The effect of JQ-1 on the expressions of BRD4, miR-106b-5p and P21, and the effect of P21 inhibitor UC2288 on the expressions of P21 and BRD4 were detected. Kras WT TPC-1 cells were divided into JQ-1+ NC-OE group, JQ-1+ p21-OE group (overexpression of p21) and JQ-1+ p21-OE+ miR-106b-5p mimic group (overexpression of p21 and miR-106b-5 at the same time), and the proliferation, invasion and apoptosis of cells in each group were detected. TPC-1 cells were divided into Kras WT group, Kras WT+ JQ-1 group, Kras G12D group and Kras G12D+ JQ-1 group, and the cell proliferation, invasion and apoptosis of each group were detected. Results:JQ-1 inhibited the proliferation activity of Kras WT TPC-1 cells in a dose-dependent and time-dependent manner. In the NC group and JQ-1 group, the numbers of cell invasion were 124.67±9.61 and 82.67±8.02, and the apoptosis rates were (5.91±0.34)% and (10.33±1.10)%, respectively, with statistically significant differences ( t=5.812, P=0.004; t=6.653, P=0.003). JQ-1 significantly inhibited the expressions of BRD4 and miR-106b-5p, and promoted the expression of P21 in Kras WT TPC-1 cells. UC2288 significantly inhibited P21 expression, but had no significant effect on BRD4 expression. In the JQ-1+ NC-OE group, JQ-1+ p21-OE group and JQ-1+ p21-OE+ miR-106b-5p mimic group, the proliferation activities at 24 h of Kras WT TPC-1 cells was 0.46±0.03, 0.35±0.04 and 0.44±0.03 ( F=8.720, P=0.017), and the proliferation activity of JQ-1+ p21-OE group was significantly lower than that of the JQ-1+ NC-OE group ( P<0.05). The numbers of cell invasion in the three groups were 83.00±9.17, 56.67±6.03 and 79.67±10.07 ( F=8.347, P=0.018), and the number of cell invasion in the JQ-1+ p21-OE group was significantly lower than that in the JQ-1+ NC-OE group ( P=0.009). The apoptosis rates of the three groups were (10.00±0.49)%, (15.39±1.14)% and (10.32±0.80)% ( F=37.764, P<0.001), and the apoptosis rate of the JQ-1+ p21-OE group was significantly higher than that in the JQ-1+ NC-OE group ( P<0.001). There were no significant differences in cell proliferation activity, invasion number and apoptosis rate between JQ-1+ p21-OE+ miR-106b-5p mimic group and JQ-1+ NC-OE group (all P>0.05). In Kras WT group, Kras WT+ JQ-1 group, Kras G12D group and Kras G12D+ JQ-1 group, the cell proliferation activities at 24 h were 0.50±0.05, 0.39±0.04, 0.68±0.08 and 0.64±0.05 ( F=17.776, P<0.001). Compared with the Kras WT group, cell proliferation activity in the Kras WT+ JQ-1 group was significantly decreased, while that in the Kras G12D group was significantly increased (both P<0.05). The numbers of cell invasion in the four groups were 129.33±11.50, 86.00±9.54, 161.67±13.01 and 146.33±13.20 ( F=22.598, P<0.001). Compared with the Kras WT group, the number of cell invasion in the Kras WT+ JQ-1 group was significantly decreased ( P=0.002), and that in the Kras G12D group was significantly increased ( P=0.010). The apoptosis rates in the four groups were (6.17±0.50)%, (10.42±0.73)%, (3.43±0.47)% and (3.41±0.32)% ( F=119.170, P<0.001). Compared with the Kras WT group, the apoptosis rate in the Kras WT+ JQ-1 group was significantly increased ( P<0.001), and that in the Kras G12D group was significantly decreased ( P<0.001). There were no significant differences in cell proliferation activity, invasion number and apoptosis rate between Kras G12D+ JQ-1 group and Kras G12D group (all P>0.05). Conclusion:BRD4 inhibitor can specifically inhibit the development of wild-type Kras DTC via regulating the molecular axis of BRD4/miR-106b-5p/P21, but has no significant effect on the proliferation, invasion and apoptosis of mutant Kras DTC tumor cells.
4.Bibliometric analysis for research hotspot and frontier of ursolic acid
Jun ZHAO ; Xiaolei ZHANG ; Beibei NI ; Xue YANG ; Kai WANG ; Chuanzhou ZHANG ; Guangwei LIU
China Pharmacy 2022;33(17):2102-2107
OBJECTIVE To e xplore the research hots pots and development frontiers of ursolic acid in recent 20 years,and to provide reference for researchers in this field. METHODS Research literatures related to ursolic acid in Web of Science from Jan. , 1,2002 to Dec. 31,2021 were collected ,and visualization analysis was performed on countries or regions ,research institutions , authors,journals and keywords involved in the literatures using CiteSpace software ,to obtain the spatial and temporal distribution of ursolic acid and research frontiers. The research status and development frontier of ursolic acid were further analyzed by analyzing keywords co-occurrence ,keyword emergence ,keyword clustering ,etc. RESULTS & CONCLUSIONS Totally 3 528 valid papers were included in this study ,and the top three countries were China ,India and the United States. Analysis of publishing institutions showed that Chinese Academy of Sciences ,Univisity of Karachi and China Medical University were the top 3 research institutions in the list of publication amount. Analysis of published journals showed that Molecules (127 articles),Journal of Ethnopharmacology(90 articles),Journal of Agricultural and Food Chemistry (75 articles)had high number of literatures on ursolic acid. The analysis of keyword analysis showed that pharmacological effects ,such as antitumor activity of ursolic acid , antioxidant activity ,antibacterial activity and anti-inflammatory activity ,are always the focus of the research ;the mechanism ursolic acid induced apoptosis ,oxidative stress and autophagy ,the research on ursolic acid signaling pathway ,drug delivery of ursolic acid nanoparticles were the research direction in the future.
5.Correlation between KRAS genemutationandDTC resistance to 131I radiotherapy and prognosis
FENG Zhiping ; CHEN Fukun ; YANG Chuanzhou ; CHEN Ting ; ZHU Jialun ; LIU Chao ; LV Juan ; LU Jianmei ; DENG Zhiyong
Chinese Journal of Cancer Biotherapy 2019;26(2):213-219
Objective: To investigate the correlation between KRAS gene mutation and differentiated thyroid carcinoma (DTC) treatment effect and prognosis, and to explore the mechanism. Methods: Clinical tissue samples from DTC patients undergoing 131I Radiotherapy were collected. Then single strand conformation polymorphism analysis of polymerase chain reaction products (PCRC-SSCP) was used to detect KRAS mutation rate in thyroid cancer patients of different TNM stages; p21 protein expression level was detected by real-time quantitative polymerase chain reaction (qPCR) and western blotting. DTC cells were treated by sub-lethal dose of 131I Radiotherapy, and then CCK-8 assay, transwell assay and flow cytometry (FCM) were used to evaluate the changes of cells viability. Animal models were then constructed for verification. Results: The results showed that KRAS gene mutants were increased in 131I-resistant DTC patients; KRAS gene mutation suppressed p21 protein expression and was associated with clinical stage and poor prognosis. In vivo and in vitro experiments proved that sub-lethal dose of 131I increased KRAS gene mutation rate, suppressed p21 expression level, and caused 131I radiotherapy resistance. Reversely, over-expression of KRAS gene could significantly increase p21 expression, and inhibit tumor proliferation and metastasis. Conclusion: KRAS gene mutations were associated with DTC TNM stages and 131I resistance in DTC patients. Sub-lethal dose of 131I treatment could improve 131I resistance in DTC cells line, inversely, over-expressed KRAS gene could increase the sensitivity to 131I radiotherapy in DTC patients.