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1.
几种植物来源不同作用机制的抗癌药抗侵袭作用 总被引:4,自引:0,他引:4
用细胞培养法和癌细胞侵袭实验,观察几种植物来源不同作用机理的抗癌药如紫杉醇、三尖杉酯碱、高三尖杉酯碱及喜树碱[1],对黑色素瘤高转移株B16-BL6细胞及人纤维肉瘤细胞HT-1080的细胞毒作用和抗侵袭作用。结果表明紫杉醇、三尖杉酯碱、高三尖杉酯碱及喜树碱对B16-BL6和HT-1080细胞增殖均有很强的抑制作用。紫杉醇、三尖杉酯碱及高三尖杉酯碱对B16-BL6细胞侵袭和运动也有明显的抑制作用,而喜树碱在同样浓度下对B16-BL6细胞侵袭和运动均无明显抑制。 相似文献
2.
目的: 探讨caspase 3抑制剂Ac-DEVD-CHO对caspase 3和NF-κB信号转导途径的影响。方法:采用MTT法测定细胞的增殖活力,琼脂糖凝胶电泳观察细胞凋亡,流式细胞仪进行细胞周期分析,Western blotting和DIG-EMSA研究细胞凋亡途径。结果:Caspase 3抑制剂Ac-DEVD-CHO可抑制羟基喜树碱(HCPT)对Bcap-37诱导的凋亡,抑制Pro-caspase 3的裂解,并能抑制IκBα 蛋白降解,阻止NF-κB活化。结论:Caspase 3抑制剂Ac-DEVD-CHO除特异性抑制Pro-caspase 3的裂解外,还可以抑制HCPT对Bcap37细胞NF-κB的活化。 相似文献
3.
Induction of apoptosis in multi-drug resistant (MDR) human glioblastoma cells by SN-38, a metabolite of the camptothecin derivative CPT-11 总被引:5,自引:0,他引:5
Shouji Nakatsu S. Kondo Yasuko Kondo Dali Yin John W. Peterson Rami Kaakaji Tatsuo Morimura Haruhiko Kikuchi Juji Takeuchi Gene H. Barnett 《Cancer chemotherapy and pharmacology》1997,39(5):417-423
The overexpression of the multidrug resistance (mdr1) gene and its product, P-glycoprotein (P-gp), is thought to limit the successful chemotherapy of human tumors. Recent studies
demonstrate that SN-38, a metabolite of the camptothecin (CPT) derivative CPT-11, has antitumor effects on several tumors,
but the mechanisms responsible for its cytotoxicity remain unclear. We therefore determined whether SN-38 has cytotoxic effects
on MDR human glioblastoma GB-1 cells and non-MDR human glioblastoma U87-MG cells. Furthermore, we determined what role SN-38
plays in the induction of cytotoxicity in these tumor cells. In this study, we demonstrated that SN-38 had significantly stronger
antitumor effects on GB-1 and U-87MG cells than did CPT (P<0.01 and P<0.05, respectively). In addition, findings obtained using a DNA fragmentation assay, Hoechst 33258 staining, in situ end-labeling
and cell cycle analysis demonstrated that SN-38 induced apoptosis in these tumors. Our results suggest that SN-38 has a stronger
antitumor effect on malignant glioma cells regardless of MDR expression than does CPT, and therefore can be considered a new
chemotherapeutic agent potentially effective in the treatment of human primary or recurrent malignant gliomas resistant to
chemotherapy.
Received: 6 October 1995/Accepted 29 June 1996 相似文献
4.
DNA拓扑异构酶Ⅰ抑制剂诱导鼻咽癌上皮细胞凋亡的实验研究 总被引:1,自引:0,他引:1
拟从细胞凋亡角度出发,探讨能够诱导鼻咽癌上皮细胞凋亡的因素,为有效地防治该恶性肿瘤提供新的思路。方法:光镜下观察细胞的形态变化;流式细胞仪检测细胞周期变化及亚二倍体比例;DNA凝胶电泳及二苯胺法测定DNA片段化程度。结果:一定浓度的拓朴异构酶Ⅰ(Topoiso-meraseⅠ,TOPOⅠ)抑制剂喜树碱(Camptothecin,CPT)体外作用于人低分化鼻咽癌上皮细胞系CNE-2Z细胞一定时间后,镜下可见细胞体积缩小,染色质凝聚,胞膜突起及凋亡小体形成等形态变化。2~10μmol/L的CPT分别作用12小时后作流式细胞仪检测,亚二倍体比例均为30%左右;各浓度分别作用24小时,亚二倍体比例均为50%左右;同时细胞周期有明显的变化,主要表现为G2/M期细胞减少。DNA琼脂糖凝胶电泳呈典型的梯形带。结论:拓朴异构酶Ⅰ抑制剂CPT对人低分化鼻咽癌上皮细胞具有明显的凋亡诱导作用。 相似文献
5.
羟基喜树碱对肠癌细胞体外作用的研究 总被引:1,自引:1,他引:1
目的探讨羟基喜树碱对肠癌细胞的体外作用。方法 :采用改良的MTT法检测了 78例肠癌细胞对 5种化疗药物的体外敏感性。结果 :78例肠癌细胞对化疗药物的敏感性 ,由高到低依次为羟基喜树碱 (HCPT)、5-氟脲嘧啶 (5 -Fu)、丝裂霉素 (MMC)、平阳霉素 (PYM)、长春新碱 (VCR)。HCPT和 5 -Fu的敏感性差异无显著性 (P >0 .0 5 ) ,但均明显高于MMC、PYM及VCR(均P <0 .0 0 1) ,对 5 -Fu不敏感的病例中 ,5 7.8%对HCPT敏感或中度敏感。结论 :HCPT和 5 -Fu皆可作为肠癌的首选化疗药物 ,如果 5 -Fu耐药 ,则可选用HCPT。正确取材是MTT法成功的关键。 相似文献
6.
Chao Zheng Ming-Zong Li Wei-Ping Tang Li-Guang Lou 《Journal of Asian natural products research》2019,21(1):51-61
A series of E-ring lactone-opened camptothecin (CPT) derivatives bearing with terminal aza-heterocyclic groups were synthesized, and their antitumor activity was evaluated both in vitro and in vivo. Hydroxyl-amide analogues with morpholin-4-yl displayed excellent antitumor activity in vitro and efficient inhibition on tumor xenograph model in nude mice. Ester-amide compounds acted less active in vitro cytotoxicity and lower inhibition activity in vivo. Substitutions at 7- and 10- positions favored the antitumor activity. 相似文献
7.
目的 探讨羟基喜树碱(HCPT)对体外培养大鼠肝星状细胞(HSC)的增殖与凋亡的影响.方法 大鼠肝星状细胞(HSC-T6)和大鼠正常肝细胞(BRL-3A)分别在实验组(分别以含HCPT浓度为0.008、0.016、0.031、0.063、0.125,0.25、0.5、1、2、4、8、16、32mg/L的培养液培养)和对照组(单纯培养)体外培养24 h.用四甲基偶氮唑盐法检测细胞增殖情况,找出HCPT对HSC-T6细胞增殖抑制的最佳作用浓度;流式细胞仪检测细胞凋亡率;透射电子显微镜下观察细胞凋亡的形态学变化情况;琼脂糖凝胶电泳法检测DNA片段化.多个样本均数的比较采用单因素方差分析,两样本均数的比较采用t检验.结果 HCPT对HSC-T6细胞和BRL-3A细胞的增殖抑制率随着药物浓度的升高而逐渐升高;当HCPT浓度>0.5mg/L时,对BRL-3A细胞的毒性作用显著增高(P值均<0.05);0.5 mg/L对HSC-T6细胞增殖抑制作用最大,为HCPT对HSC-T6细胞增殖的最佳抑制浓度.0.125、0.25、0.5 mg/L的HCPT作用HSC-T6细胞24h,流式细胞仪检测显示细胞凋亡率分别为13.46%±2.42%、26.25%±5.65%、47.05%±8.76%,与对照组(4.89%±1.80%)相比,差异有统计学意义(F=34.24,P<0.01).0.5mg/L的HCPT作用HSC-T6细胞24 h,透射电子显微镜下可见细胞体积缩小,核仁消失,染色质浓缩聚集成团块状,沿核膜排列等凋亡形态学改变;琼脂糖凝胶电泳可见明显的DNA梯度带形成.结论 HCPT在体外可以明显地抑制HSC-T6细胞的增殖、诱导HSC-T6细胞凋亡,作用强度呈剂量依赖性. 相似文献
8.
目的 探索顺铂(DDP)时辰给药与常规给药合并羟基喜树碱(HCPrr)治疗晚期非小细胞肺癌的疗效和副作用。方法 59例Ⅲb~Ⅳ期非小细胞肺癌患者随机分为两组,顺铂时辰给药合并羟基喜树碱组(时辰化疗组)和顺铂、羟基喜树碱常规给药组(常规化疗组),两组顺铂和羟基喜树碱的剂量相同。顺铂14mg/(m2·d)。羟基喜树碱6mg/(m2·d),两药连用5天,21天为1周期,时辰化疗组顺铂在18:00用药。其他用药时间相同。每例连用两周期以上评价疗效。结果 时辰化疗组PR13例,SD13例,PD4例,有效率(CR+PR)43.3%,常规化疗组PR9例,SD17例,PD3例,有效率31.0%,两组比较P=0.051。时辰化疗组中位生存期6.62个月,12个月生存率30.4%(9/30例),18个月生存率13.3%(4/30)。常规化疗组中位生存期5.06个月,12个月生存率24.1%(7/29),18个月生存率3.4%(1/29);时辰化疗组的有效率和生存期较常规组有优势。血液学毒性和消化系统等副作用两组相仿。结论 顺铂时辰给药合并羟基喜树碱治疗晚期非小细胞肺癌有临床应用价值。 相似文献
9.
C. Bradley Hare Gertrude B. Elion Peter J. Houghton Janet A. Houghton Stephen Keir Susan L. Marcelli Darell D. Bigner H. S. Friedman 《Cancer chemotherapy and pharmacology》1996,39(3):187-191
Therapy of patients with malignant central nervous system tumors is frequently unsuccessful, reflecting limitations of current
surgical, radiotherapeutic, and pharmacotherapeutic treatments. The camptothecin derivative irinotecan (CPT-11) has been shown
to possess antitumor activity in phase II trials for patients with carcinoma of the lung, cervix, ovary, colon, or rectum
and for patients with non-Hodgkin’s lymphoma. The current study was designed to test the efficacy of the drug against a panel
of human tumor xenografts derived from adult and pediatric central nervous system malignancies. Tumors included childhood
high-grade gliomas (D-212 MG, D-456 MG), adult high-grade gliomas (D-54 MG, D-245 MG), medulloblastomas (D341 Med, D487 Med),
ependymomas (D528 EP, D612 EP), and a rhabdomyosarcoma (TE-671), as well as sublines with demonstrated resistance to busulfan
(D-456 MG (BR)), cyclophosphamide (TE-671 CR), procarbazine (D-245 MG (PR)) or melphalan (TE-671 MR), growing subcutaneously
and intracranially in athymic nude mice. In replicate experiments, CPT-11 was given at a dosage of 40 mg/kg per dose via intraperitoneal
injection in 10% dimethylsulfoxide on days 1–5 and 8–12, which is the dosage lethal to 10% of treated animals. CPT-11 produced
statistically significant (P<0.001) growth delays in all subcutaneous xenografts tested, including those resistant to busulfan, cyclophosphamide, procarbazine,
and melphalan, with growth delays ranging from 21.3 days in D487 Med to 90+ days in several tumor lines. Further, tumor regression
was evident in every treated animal bearing a subcutaneous tumor, with some xenografts yielding complete tumor regression.
Statistically significant (P<0.001) increases in survival were demonstrated in the two intracranial xenografts – D341 EP (73.0% increase) and D-456 MG
(114.2% increase) – treated with CPT-11. These studies demonstrate that, of over 40 drugs evaluated in this laboratory, CPT-11
is the most active against central nervous system xenografts and should be advanced to clinical trial as soon as possible.
Received: 4 December 1995/Accepted: 18 May 1996 相似文献
10.
Camptothecin (CPT) has heen recognized as a topoisomerase I (Topo I) inhibitor. However, the mechanism of cytotoxicity of this agent remains unknown. In the present study, we analyzed the kinetics of Topo I-mediated DNA single-strand breaks and internucleosomal DNA cleavage produced by CPT and its derivative, 7-ethyl-10-hydroxycamptothecin (SN-38), in HL-60 cells. DNA single- strand breaks were detected using alkaline sucrose gradient centrifugation when HL-60 cells were incubated with 10 μM CPT or 10 μM SN-38 for 30 min. These DNA single-strand breaks were rapidly repaired after drug removal, while the cytotoxic action of these drugs was sustained. Treatment of HL-60 cells with CPT or SN-38 for 3 h produced extensive degradation of DNA. Agarose gel electrophoresis showed a ladder of DNA fragments consisted of multimers of approximately 200 base pairs, characteristic of apoptosis. Interestingly, this type of DNA fragmentation was also induced within 4 h after repair of DNA single-strand breaks, and subsequently loss of cell viability was observed. When zinc ion, a potent inhibitor of endonuclease, was added to drug-free medium after treatment with CPT or SN-38, internucleosomal DNA cleavage was abolished. Furthermore, addition of zinc ion reduced the loss of cell viability. These data suggest that Topo I-mediated DNA single-strand breaks may be necessary but are not sufficient for cell death, and the endonuclease involved in induction of internucleosomal DNA cleavage may play an important role in HL-60 cell death induced by Topo I inhibitor. 相似文献