1.Experimental Study on Anti-tumor Prescription Screening and Therapeutic Effects of Shengma Combined with Zao Jiao-ci
Hongru LI ; Bei ZHAO ; Gangjun DU
Chinese Journal of Information on Traditional Chinese Medicine 2013;(8):32-35
Objective To screen the anti-tumor prescription (Shengzao Fang) of Shengma (Rhizoma Cimicifugae) combined with Zao Jiao-ci (Spina Gleditsiae), and evaluate its anti-tumor effects. Methods The lung metastatic model of 4T1 breast cancer and the 4T1 subcutaneous transplanted model were established, both models of mice were randomly divided into model group, Shengma group, Zao Jiao-ci group, Shengzao Fang first group, Shengzao Fang second group and Shengzao Fang third group, 10 mice for each group. The proportion of Shengzao Fang was ascertained by their anti-tumor effects. MTT assay was used to investigate the effects of Shengzao Fang on 4T1 breast cancer. The concentration of type 1 collagen (Col-Ⅰ), platelet-activating factor (PAF), tissue inhibitor of metalloproteinase 1 (TIMP-1), tyrosine kinase receptor A (TrkA) and tyrosine kinase receptor B (TrkB) in serum from tumor-bearing mice was tested by enzyme-linked immunosorbent assay (ELISA). The effects of Shengzao Fang on matrix metalloproteinase (MMPs) was examined by Gelatin matrix method. Results Compared with the model group, the prescription of Shengma∶Zao Jiao-Ci=2∶1 significantly suppressed lung metastasis of 4T1 breast cancer, showing fewer lung nodes, lower lung metastasis rate and highest tumor inhibitory rate to 4T1 subcutaneous transplanted model. Although the concentration of serum Col-Ⅰ, PAF, TIMP-1, TrkA and TrkB was decreased in all treated group, the prescription of Shengma∶Zao Jiao-ci=2∶1 had the strongest activity, and its inhibitory effect on the expression of MMP-2 and MMP-9 was strongest, too. Conclusion The prescriptions of Shengma combined with Zao Jiao-ci had different antitumor activity, the strongest activity was exhibited when shengma∶Zao Jiao-ci was 2∶1, suggesting that 2∶1 was optimization for Shengma combined with Zao Jiao-ci.
2.Breviscapine promotes K562 cell apoptosis induced by doxorubicin
Gangjun DU ; Haihong LIN ; Qitai XU
Chinese Pharmacological Bulletin 2003;0(08):-
Aim To observe effects of breviscapine on lymphocyte proliferation and K562 cell death caused by doxorubicin.Methods The cell proliferation was tested by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)assay,the p53/bcl-2 expression were assessed by western blotting,cell apoptosis was quantitated by Histone/DNA ELISA and flow cytometry,cytochrome C release was determined by ELISA,caspase-8 and caspase-3 activation were examined by colorimetric assay.Results Breviscapine could obviously enhance mouse lymphocyte proliferation and its resistance to doxorubicin,promote growth inhibition,cytochrome C release,caspase-8 and caspase-3 activation in K562 cells which were caused by doxorubicin,upregulate radio of p53/bcl-2 expression,and increase cell apoptosis.Conclusion Breviscapine was able to enhance antitumor effect of doxorubicin,the major mechanism by which breviscapine could promote sensitivity of tumor cell to chemotherapeutic agents might be related to activated apoptosis signal way.
3.Antitumor action of methylene blue
Qitai XU ; Gangjun DU ; Baiquan CHEN ;
Chinese Pharmacological Bulletin 1987;0(03):-
5.Protective action of breviscapine against bleomycin-induced lung fibrosis in mice
Gangjun DU ; Shuo ZHANG ; Haihong LIN ; Mei WANG ; Liyan JI
Chinese Pharmacological Bulletin 1987;0(02):-
Aim To observe the protective effects of breviscapine against lung fibrosis and investigate its possible mechanism.Methods Effects of breviscapine on cell proliferation,activation and extracellular matrix secretion were examined in mouse embryonic lung fibroblast L929 cells in vitro.The mouse model of bleomycin-induced lung fibrosis was used to assess the protective effect of breviscapine against lung fibrosis.Results In vitro,breviscapine had no cytotoxicity directly on L929 cells,however,it could suppress cell proliferation,activation and secretion of laminin(LN) and collagen Ⅰ(ColⅠ) induced by transforming growth factor beta1(TGF-?1) in L929 cells.In vivo,breviscapine could prevent increase in serum TGF-?1 and decrease in superoxide dismutase(SOD),peroxidase(POD) and catalase(CAT) in mice with lung fibrosis caused by bleomycin.In addition,breviscapine was able to reduce pulmonary hydroxyproline,collagen,malondialdehyde(MDA)and TGF-?1 in lung fibrosis mice.Conclusion Breviscapine has protective effect against lung fibrosis and the possible mechanism is to enhance antioxidative defense activities and prevent TGF-? signal.
6.Effect of lacidophilus exopolysaccharides on immunity
Qitai XU ; Yu ZHANG ; Gangjun DU ; Baiquan CHEN ; Cuiping BAO
Chinese Pharmacological Bulletin 2003;0(12):-
Aim To study the effect of Lacidophilus exopolysaccharides(LAEPS) on immunity. Methods Effects of LAEPS on immunity were investigated by delayed type hypersensitivity reaction, haemolytic plaque assay and macrophage function assay in mice. Results LAEPS ip 7~8 day promoted delayed type hypersensitivity reaction, increased haemolytic plaque and enhanced macrophage function in a dose-dependent manner.Conclusion LAEPS is able to enhances immunity.
8.Study on antiangiogenesis and antitumor of thalidomide
Gangjun DU ; Haihong LIN ; Qitai XU ; Minwei WANG ; Yiming YANG
Chinese Pharmacological Bulletin 1986;0(04):-
Aim To study antiangiogenesis and antitumor of thalidomide.Methods In HUVECs, cell viability was determined by MTT assay;death type was observed by electron microscope; ratio of apoptosis was quantitated by flow cytometry.Angiogenesis was tested in chicken embryo chorioallantoic membrane.Effect of thalidomide on S_(180) was examined in homograft mice and microvascular counts were detected through immunochemical staining method.Results Thalidomide might inhibite the growth of HUVECs with a IC_(50) value of(22.91?1.74) ?mol?L~(-1),cells treated by thalidomide for 48 h displayed morphological characteristics of different stages associated with apoptosis,which were irregular nucleus, condensed chromatin, ballooning endoplasmic reticulum, apoptotic bodies,under electron microscope.Thalidomide might be able to cause apoptosis or necrosis of HUVECs in flow cytometry and raised positive of antiangiogenesis with increasing of dosage in chicken embryo chorioallantoic membrane. Thalidomide as a single agent might not significantly prevent tumor growth but decrease microvascular counts in tumors, however, in combination with cyclophosphamide, thalidomide could decrease dosage of cyclophosphamide and enhance antitumor of cyclophosphamide.Conclusion Thalidomide might hold back angiogenesis,as a single agent, could not significantly prevent S_(180) tumor from growing,but acted synergistically with cyclophosphamide.
9.The safety and efficacy of trimodality treatment for invasive bladder cancer
Fang YUAN ; Yong JIANG ; Jia DU ; Junyong DAI ; Jun LI ; Peng XIAN ; Yuan LI ; Gangjun YUAN ; Xianli TANG ; Yanping SONG ; Cheng WANG ; Nan LIU
Chinese Journal of Urology 2022;43(6):416-422
Objective:To evaluate the safety and efficacy of trimodality treatment (TMT) which is complete transurethral resection of bladder tumor with concurrent radiotherapy and chemotherapy for invasive bladder cancer.Methods:From Mar. 2016 to Oct.2021, patients who were indicated of radical cystectomy (RC) but refused were enrolled to TMT treatment prospectively. Inclusive criteria were: ① the patients refused radical surgery; ② male or female, no older than 80 years; ③ no matter the tumor size, the bladder tumor be completely resected by transurethral surgery, and the hydronephrosis be improved after resecting the tumor; ④ the postoperative pathology of urothelial carcinoma; ⑤ recurrent T 1 and high-grade non-muscle invasive bladder cancer (NMIBC) or T 2-4a muscle invasive bladder cancer (MIBC); ⑥ no definitive metastasis in preoperative chest, abdominal CT or MRI; ⑦ hemoglobin ≥100 g/L, white blood cell count ≥4×10 9/L, platelet count ≥100×10 9/L, and normal liver and renal function. The exclusion criteria were: ① tumor invading bladder neck or anterior or posterior urethra; ② bladder contracture or severe urethral stricture; ③ regional lymph node metastasis or distant metastasis by imaging examination; ④ no improvement of hydronephrosis after resection; ⑤ definitive contraindications of radiotherapy or chemotherapy; ⑥ uncontrolled hypertension, diabetes, coronary heart disease or other severe diseases. After cTURBT, paclitaxel (50 mg/m 2 on Day 1 of each week) combined with cisplatin(20 mg/m 2 on day 1-2 of each week)was administered with concurrent radiotherapy (2 Gy/fraction/day) for 4 weeks. If cystoscopy and/or radiographic detected no recurrence or metastasis, the patients were treated with concurrent chemoradiotherapy for 2 and a half weeks (total dose of 64 Gy). The side effects of radiotherapy and chemotherapy during TMT were observed, the quality of life(QOL)was evaluated by FACT-P scale, and the bladder recurrence, distant metastasis and survival were assessed with imaging and cystoscopy. From March 2016 to October 2021, 79 patients with RC were enrolled, including 67 males and 12 females, aged 44-86 years. The pathology of RC was urothelial carcinoma of the bladder. There was no definitive lymph node or distant metastasis in preoperative imaging. The progress and survival after TMT and RC treatment were followed up and the survival rates were calculated by Kaplan-Meier method. Results:Of the 30 patients who underwent TMT, including 25 males and 5 females, aged 32-76 years, there were 7 cases of cT 1 (23.3%), 19 cases (63.3%) of cT 2, 2 cases of cT 3 (6.7%)and 2 cases of cT 4(6.7%), respectively. A total of 132 adverse events of all grades of chemoradiotherapy occurred, of which only 4 were grade Ⅳ, with no bowel leakage or death due to complications. The mean scores of negative questions in FACT-P were 3.22±0.67, 1.30±0.63 and 0.87±0.69 before TMT treatment, 6 and 12 months after TMT treatment, respectively. The quality of life was significantly improved( F=129.081, P<0.001), and the rate of bladder preservation was 86.7%(26/30). Two cases underwent salvage RC(6.7%)and 2 cases died of bladder recurrence(6.7%). There were 8, 4 and 2 patients survived 4, 5 and 6 years, respectively. Seven cases (23.3%) had bladder recurrence, 3 cases (10.0%) underwent distant metastasis and 6 patients (20.0%)died after TMT because of the progression. The 1, 2 and 5 year overall survival rates by TMT treatment were 88.89%, 82.96% and 62.77%, respectively. Median follow-up was 19.5(6.8-44.5) months in the TMT group and 35.5(18.8-53.3) months in the RC group ( z=-1.998, P=0.046). Progression-free survival in the TMT and RC group were 66.7% and 80.0%( χ2=1.047, P=0.306), and the overall survival rates were 80.0% and 80.0% ( χ2=0.482, P=0.488) respectively. The difference was not statistically significant. Conclusions:The TMT is a safe and effective alternative for RC, which can improve the quality of life and control the tumor sufficiently.