丝裂霉素、5-氟尿嘧啶、三苯氧胺联合应用对人乳癌细胞株的作用

目的：观察丝裂霉素、5-氟尿嘧啶、三苯氧胺联合应用对人乳腺癌细胞株(MDA—MB—435S)的相互作用。方法：采用MTT法利用中效原理判断联合用药的效应。结果：MMC、5—Fu单用及联合应用时，随着药物浓度增加其效应也增加；TAM与MMC、5—Fu合用时，对MDA—MB—435S细胞作用不明显；MMC与5—Fu高浓度合用时呈协同作用，低浓度时呈拮抗作用；两药合用时浓度比例变化及给药时间次序对效应影响不大。结论：MMC与5—Fu高浓度合用时为协同作用，低浓度时为拮抗作用。TAM与MMC、5—Fu合用时，对MDA—MB—435S细胞作用不明显。两药合用效应大小与两药浓度比例及给药时向次序无关。     

顺铂、5-氟尿嘧啶、长春新碱配伍对人肝癌细胞株(7721)的相互作用

目的:观察顺铂、5-氛尿嘧啶、长春新碱配伍在体外对人肝癌细胞株(7721)的相互作用.方法:采用MTT法利用中效原理判定两药合用的效果.结果:3种药物单独应用时随着药物剂量增加,其效应也增加;两药大剂量(大于中效剂量)合用时可产生拮抗作用(CI>1);小剂量(小于中效剂量)合用时可产生协同作用(CI>1);两药合用时的浓度比例及给药时间次序不同均会影响效应大小.结论:上述3种药物任何两种合用小剂量产生协同作用,大剂量产生拮抗作用,且效应大小与两药浓度比例及给药时间次序有关.     

苦参碱与3种抗肿瘤药物联合作用对KBV200耐药细胞株细胞周期的影响

目的:探讨苦参碱分别与3种常用抗肿瘤药物长春新碱(VCR)、阿霉素(ADM)、顺铂(DDP)合用对KBV200耐药细胞株细胞周期的影响。方法:将培养后的KBV耐药细胞分为对照组、抗肿瘤药物组及其与苦参碱合用组,采用流式细胞仪检测、分析各组细胞周期的变化及凋亡情况。结果:与抗肿瘤药物单用组比较,苦参碱与VCR、ADM合用组细胞处于不同周期的细胞比例及凋亡数均无明显变化;苦参碱与DDP合用组G0~G1期细胞数下降、G2~M期细胞数升高。结论:推测苦参碱逆转KBV200细胞对VCR和ADM的耐药作用可能与细胞周期及凋亡无关;苦参碱能轻度增强DDP的细胞毒作用。     

紫杉醇联合抗HER2单抗对人卵巢癌细胞株A2780的作用

目的:体外观察紫杉醇及抗HER2单抗对人卵巢癌细胞株A2780增殖的抑制作用及两者联合应用时的抑制率及相互作用.方法:采用MIT法测定两者单用或合用对A2780的增殖抑制率,利用中效原理判定两药合用的效果,用流式细胞仪观察细胞凋亡及细胞周期的变化.结果:两种药单独应用时随药物剂量增加,其效应也增加,紫杉醇的中效浓度为6.98 nmol·L-,抗HER2单抗的中效浓度为8.69 μg·ml-1;两药合用时它们的中效浓度为2.92 nmol·L-1 0.49 μg·ml-.大剂量(紫杉醇＞13.02 nmol·L-,抗HER2单抗＞2.17 μg·ml-1)合用时是拮抗作用(CI＞1),小剂量(紫杉醇＜13.02 nmol·L-,抗HER2单抗＜2.17 μg·ml-1)合用时是协同作用(CI＜1).结论:紫杉醇联合抗HER2单抗对人卵巢癌细胞株A2780的生长有抑制作用,它们合用时大剂量是拮抗,而小剂量则为协同作用.     

表柔比星、羟喜树碱、顺铂对人膀胱癌细胞株的相互作用

目的观察表柔比星(epirubicin,EPI、羟喜树碱(hydroxy-camptothecin,HCPT)、顺铂(cisplatinum,DDP)在体外对人膀胱癌细胞株(T24)的相互作用.方法采用四甲基偶氮唑蓝(MTT)法利用中效原理判断药物联合应用的效果及药物对膀胱癌细胞株粘贴力的影响.结果3种药物单独应用随着药物剂量的增加,其效应也增加;EPI与HCPT或DDP联合时,两药大剂量(大于中效剂量)合用时可产生拮抗作用,小剂量(小于中效剂量)合用时可产生协同作用;HCPT与DDP联合时,在适当剂量(中效剂量×10-2～中效剂量)合用时可产生协同作用;两药合用时的浓度比例及给药时间次序不同均会影响效应的大小;3种药物单用或合用均会使肿瘤细胞粘贴力下降,其下降程度与用药配伍情况有关.结论两种药物合用时可以产生协同或拮抗作用,且效应大小与两药浓度比例及给药时间次序有关;3种药物均可降低肿瘤细胞的侵袭能力.     

丝裂霉素C联合原花青素对人膀胱癌BIU87细胞的生长抑制作用

［摘要］目的探讨丝裂霉素C（MMC）与葡萄籽提取物原花青素（grape seed procyanidin extract, GSPE）联合应用对人膀胱癌BIU87细胞的生长抑制作用。方法采用噻唑蓝（MTT）比色法测定MMC和GSPE单独和联合应用时对人膀胱癌BIU87细胞生长的抑制作用,并应用Chou Talalay联合指数法定量分析药物之间的相互作用效果。结果MMC、GSPE单独应用时,BIU87细胞生长的抑制作用随药物浓度的增加而增加,中效浓度分别为15.422,195.865 μg•mL 1。MMC与GSPE联合应用时,作用效果表现为在低浓度（0%＜fa＜37%）时呈协同作用（CI＜1）,高浓度（37%＜fa＜100%）时呈拮抗作用（CI＞1）,中效浓度为109.496 μg•mL 1 （其中MMC 8.111 μg•mL 1,GSPE 101.385 μg•mL 1）。结论MMC和GSPE相互作用的效果在低浓度时呈协同作用,高浓度时呈拮抗作用。     

三氧化二砷联合木黄酮对人胃癌细胞株SGC-7901的作用

目的:体外观察三氧化二砷及木黄酮对人胃癌细胞株(SGC-7901)的相互作用。方法:采用MTT法检测药物效应,利用中效原理判定两药合用的效果。结果:两种药单独应用时随着药物剂量增加,其效应也增加,呈剂量-效应关系;两药合用时合用指数均小于1(CI<1)。结论:三氧化二砷联合木黄酮对人胃癌细胞株SGC-7901的作用是协同作用。     

野木瓜果实总皂苷对BEL-7402/5 FU细胞多药耐药性的逆转作用

目的 研究野木瓜果实总皂苷对人肝癌耐药细胞BEL-7402/5 FU多药耐药(MDR)的逆转作用,并初步探讨其耐药逆转机制.方法 采用MTT法测定5-氟尿嘧啶(5-FU)、阿霉素(ADM)、丝裂霉素(MMC)和野木瓜果实总皂苷对BEL-7402细胞、BEL-7402/5 FU细胞的毒性及野木瓜果实总皂苷逆转MDR的效果;利用蛋白质印迹法检测P-糖蛋白(P-gp)的表达情况.结果 BEL-7402/5 FU细胞对5-FU、ADM、MMC的耐药指数分别为21.71,2.73,2.11;野木瓜果实总皂苷能有效抑制BEL-7402/5 FU细胞增殖,无细胞毒性剂量为5,10 μg/mL,逆转耐药倍数分别为1.36、1.93;野木瓜果实总皂苷联合5-FU作用BEL-7402/5 FU细胞,可降低P-gp蛋白表达.结论 野木瓜果实总皂苷能部分逆转BEL-7402/5 FU细胞MDR,其机制可能是通过下调P-gp的表达而实现的.     

甲基莲心碱对MCF-7细胞体外化疗增敏作用

目的 :探讨甲基莲心碱 ( Neferine,Nef)的体外化疗增敏作用。方法 :以人乳腺癌细胞 MCF- 7为研究对象 ,MTT法测定药物的细胞生长抑制率 ,流式细胞仪 ( Flow cytometry,FCM)检测细胞凋亡。结果 :Nef( 5 um ol· L- 1 、10 um ol· L- 1 )分别与阿霉素 ( ADM)、5 -氟尿嘧啶 ( 5 - FU )、顺铂 ( CDDP)合用 ,可增加它们对 MCF- 7细胞的生长抑制率 ,q>1。Nef( 10 um ol· L- 1 可增强 10 umol· L- 1 ADM诱导 MCF- 7细胞凋亡的作用。结论 :Nef具有化疗增敏作用。     

吉西他滨和依托泊苷联合应用对人卵巢癌3AO细胞系的作用

目的：观察吉西他滨和依托泊苷联合应用对人卵巢癌3AO细胞系的抑制效应,并初步探讨其作用机制。方法：用MTT法检测化疗药物对人卵巢癌3AO细胞系的抑制率（Fa）;FCM（流氏细胞术）检测肿瘤细胞周期分布和细胞凋亡。结果：吉西他滨和依托泊苷单用或合用对人卵巢癌3AO细胞系均有抑制作用,且呈剂量和时间依赖性;通过中效原理计算CI（合用指数）合用48h后,两种药物的CI〈1,呈协同作用。合用72h后,当Fa〈0.78时,合用指数CI〈1,两种药物之间是协同作用,而当Fa〉0.78时,合用指数CI〉1,两种药物之间呈拮抗作用;吉西他滨和依托泊苷二者联合应用对细胞周期没有影响,但凋亡率明显提高。结论：吉西他滨和依托泊苷单用或合用对3AO均有抑制作用,且呈剂量、时间依赖性。合用48h后,两种药物呈协同作用。合用72h后,当Fa〈0.78时,两种药物之间是协同作用,而当Fa〉0.78时,两种药物之间呈拮抗作用;吉西他滨和依托泊苷的作用均与其诱导凋亡和影响细胞周期有关,二者联合应用对细胞周期没有影响,但凋亡率明显提高。     

体外5-氟脲嘧啶及华蟾素对人胃癌细胞株的相互作用

目的:体外观察5-氟脲嘧啶(5-Fu)及华蟾素合用对人胃癌细胞株(BGC823)的相互作用.方法:采用噻唑兰(MTT)法,利用中效原理判定两药合用的效果.结果:两种药单独应用及合用时随着药物剂量和时间增加,其效应也增加.结论:两药合用时是协同作用.     

姜黄素联合木黄酮对人胃癌细胞株SGC-7901的作用

目的 :体外观察姜黄素及木黄酮对人胃癌细胞株 (SGC - 790 1)的联合作用。方法 :采用四甲基偶氮唑盐(MTT)法检测药物效应 ,利用中效原理判定两药合用的效果。结果 :两药单独应用时随着药物剂量增加 ,其效应也增加 ,呈剂量 -效应关系 ;两药合用时合用指数CI<1。结论 :姜黄素联合木黄酮对人胃癌细胞株SGC - 790 1的作用是协同作用。     

Amiloride sensitizes human pancreatic cancer cells to erlotinib in vitro through inhibition of the PI3K/AKT signaling pathway

Aim:

Blockade of EGFR by EGFR tyrosine kinase inhibitors such as erlotinib is insufficient for effective treatment of human pancreatic cancer due to independent activation of the Akt pathway, while amiloride, a potassium-sparing diuretic, has been found as a potential Akt inhibitor. The aim of this study was to investigate the anticancer effects of combined amiloride with erlotinib against human pancreatic cancer cells in vitro.

Methods:

Cell proliferation, colony formation, cell cycle and apoptosis were analyzed in 4 human pancreatic cancer cell lines Bxpc-3, PANC-1, Aspc-1 and CFPAC-1 treated with erlotinib or amiloride alone, or in their combination. The synergistic analysis for the effects of combinations of amiloride and erlotinib was performed using Chou-Talalay''s combination index isobolographic method.

Results:

Amiloride (10, 30, and 100 μmol/L) concentration-dependently potentiated erlotinib-induced inhibition of cell proliferation and colony formation in the 4 pancreatic cancer cell lines. Isobolographic analysis confirmed that combinations of amiloride and erlotinib produced synergistic cytotoxic effects. Amiloride significantly potentiated erlotinib-induced G₀/G₁ cell-cycle arrest and apoptosis in Bxpc-3 and PANC-1 cells. Amiloride inhibited EGF-stimulated phorsphorylation of AKT, and significantly enhanced erlotinib-induced downregulation of phorsphorylation of EGFR, AKT, PI3K P85 and GSK 3β in Bxpc-3 and PANC-1 cells.

Conclusion:

Amiloride sensitizes human pancreatic cancer cells to erlotinib in vitro through inhibition of the PI3K/AKT signaling pathway. Treatment of pancreatic cancer patients with combination of erlotinib and amiloride merits further investigation.     

Screening of anticancer drugs for chemoembolization of hepatocellular carcinoma

The aim of this study was to select the best candidate drug for transarterial chemoembolization by in-vitro cytotoxic evaluations of 11 anticancer drugs on three human hepatocellular carcinoma (HCC) cell lines. The SNU-398, HepG2, and SNU-449 human HCC cell lines were exposed for 30 min to 11 concentrations of doxorubicin, epirubicin, idarubicin, mitoxantrone, carboplatin, cisplatin, oxaliplatin, 5-fluorouracil, gemcitabine, mitomycin C, or paclitaxel. Cytotoxicity was measured using a quantitative colorimetric assay. For each drug and cell line, we calculated the drug concentration that caused 90% cell death (IC90). To enable comparisons of drugs with different concentration ranges, we computed the cytotoxic index (CyI) as the ratio of maximal drug concentration of more than IC90. Parameters were estimated using nonlinear regression models. Idarubicin was the most active drug on all three cell lines. With SNU-398 cells, the idarubicin CyI was 2.4-fold, 2.5-fold, 57-fold, 148-fold, and more than 58 748-fold higher than the CyIs of mitoxantrone, epirubicin, doxorubicin, gemcitabine, and other drugs, respectively. With HepG2 cells, the idarubicin CyI was 27-fold, 28-fold, 51-fold, and more than 1343-fold higher than the CyIs of doxorubicin, epirubicin, mitoxantrone, and other drugs, respectively. On the resistant SNU-449 cell line, the idarubicin CyI was 2.9-fold and 14-fold higher than the CyIs of paclitaxel and gemcitabine, respectively, the only other drugs effective on this cell line. Among 11 chemotherapeutic agents including doxorubicin, cisplatin, and epirubicin, the most effective on three HCC cell lines was idarubicin. Further clinical investigations are needed to evaluate the safety and efficacy of idarubicin for transarterial chemoembolization in HCC.     

柔红霉素长春新碱体外对人急性髓系白血病细胞株的相互作用

目的：观察柔红霉素、长春新碱联合应用在体外对人急性髓系白血病细胞株（HL－60）的相互作用。方法：采用MTT法，利用中效原理判断联合用药的效果。结果；两种药物单用及联合应用时随着药物剂量增加，其效应也增加。两药大剂量合用时为拮抗效应，较小剂量合用时为协同效应。两药合用时（除最小剂量外）与先用柔红霉素24小时或先用长春新碱24小时比较P＜0．01；小剂量合用时先用柔红霉素24小时与先用长春新碱24小时比较P＞0．05。两药合用时浓度变化会影响合用效应。结论：柔红霉素与长春新碱合用时大剂量为拮抗，较小剂量为协同；合用效应大小与两种药物浓度比例有关；与给药先后次序无关，同时给药效果好。     

顺铂与氯霉素联用增强对人肺腺癌A549细胞的抑制作用

目的体外观察顺铂和氯霉素对人肺腺癌A549细胞的相互作用。方法采用MTT法,利用中效原理判定联合应用顺铂及氯霉素对人肺腺癌A549细胞的效应。结果顺铂与氯霉素联用可以明显抑制人肺腺癌A549细胞的生长,两药单用和联用时随着药物浓度增加,其效应也增加;两药联用时的中效浓度明显小于两药单独使用时的中效浓度（顺铂减少43.8%,氯霉素减少79.1%）;两药大剂量合用时为拮抗效应（CI〉1）,小剂量合用时为协同效应（CI〈1）;并且两药合用时的效应与给药的时间先后次序无关（P〉0.05）。结论顺铂与氯霉素的联用可以明显抑制人肺腺癌A549细胞的生长,两药联用时的中效浓度较单用时明显减小;上述两种药合用时大剂量为拮抗,小剂量为协同;两药合用时的效应与给药的时间先后次序无关。     

Effect of the cisplatin-procaine complex DPR in combination with several anticancer agents on murine P388 leukemic cells in vitro and in vivo

We evaluated in vitro the antiproliferative activity of DPR (Fig. 1), a new cisplatin-derived compound, in combination with five conventional anticancer drugs: the antimetabolites 5-fluorouracil (5FU) and methotrexate (MTX), the alkylating agent mitomycin C (MMC), the antimicrotubule agent taxol (TAX) and the intercalating agent of the antracycline group doxorubicin (DOX), against murine P388 leukemic cells. MTT assay was used to determine growth inhibition after incubation of cells for 72 hours in the presence of single or combined drugs. The additive, synergistic or antagonistic nature of the combined drug effect was determined using the isobole method.In our cellular model, synergism was the prevailing result observed when DPR was combined with MMC. Conversely, antagonism was observed when DPR was combined with TAX. When DPR was administered together with the other antineoplastic drugs, the final effect was dependent on the concentrations of single agents.The study in vitro of the association between DPR and MMC was extended in vivo in BDF-1 female mice bearing ip P388 leukemic cells. Our data in vivo confirmed those obtained in vitro, demonstrating the therapeutic advantage of the association of ineffective doses of DPR (2 and 7 mg/kg) and MMC (3.2 mg/kg) over the administration of MMC alone.     

Effect of the cisplatin-procaine complex DPR in combination with several anticancer agents on murine P388 leukemic cells in vitro and in vivo

We evaluated in vitro the antiproliferative activity of DPR (Fig. 1), a new cisplatin-derived compound, in combination with five conventional anticancer drugs: the antimetabolites 5-fluorouracil (5FU) and methotrexate (MTX), the alkylating agent mitomycin C (MMC), the antimicrotubule agent taxol (TAX) and the intercalating agent of the antracycline group doxorubicin (DOX), against murine P388 leukemic cells. MTT assay was used to determine growth inhibition after incubation of cells for 72 hours in the presence of single or combined drugs. The additive, synergistic or antagonistic nature of the combined drug effect was determined using the isobole method. In our cellular model, synergism was the prevailing result observed when DPR was combined with MMC. Conversely, antagonism was observed when DPR was combined with TAX. When DPR was administered together with the other antineoplastic drugs, the final effect was dependent on the concentrations of single agents. The study in vitro of the association between DPR and MMC was extended in vivo in BDF-1 female mice bearing i.p. P388 leukemic cells. Our data in vivo confirmed those obtained in vitro, demonstrating the therapeutic advantage of the association of ineffective doses of DPR (2 and 7 mg/kg) and MMC (3.2 mg/kg) over the administration of MMC alone.