草分枝杆菌联合化疗药物对人肺癌细胞生长抑制作用的研究

目的　探讨草分枝杆菌对人肺腺癌细胞系SPCA/I的抗增殖作用以及不同浓度草分枝杆菌与化疗药物联合应用时的协同效应。方法　应用MTT比色法检测不同浓度组的草分枝杆菌以及草分枝杆菌与化疗药物联合应用对SPCA/I人肺腺癌细胞生长的抑制作用 ,波长定于 570nm ,测定光密度 (A值 )并计算其抑制率。结果　 (1 )不同浓度的草分枝杆菌体外对人肺腺癌细胞均有抑制作用 ,其抑制率随所用浓度呈正相关。 (2 ) 1 .72ug/ml及 0 .86ug/ml浓度的草分枝杆菌与化疗药物 (1PPC)联用 ,体外对人肺腺癌细胞的抑制率显著高于单用化疗药物组。结论　草分枝杆菌体外对SPCA/I人肺腺癌细胞有直接的抑制作用 ,该药与化疗药物联合应用有显著的协同抗肿瘤效应 ,其结果可能为肿瘤的临床联合化疗提供实验依据     

PI3K/Akt抑制剂LY294002对大肠癌细胞化疗增敏作用的探讨

目的 探讨PI3K/Akt特异性抑制剂LY294002与化疗药物联合使用对大肠癌细胞(HCT-8)化疗效果的影响.方法 将LY294002联合化疗药物作用于大肠癌细胞系HCT-8,MTT法检测单独使用5-Fu、奥沙利铂及联合PI3K抑制剂LY294002,对体外培养的大肠癌细胞系HCT-8增殖的抑制作用,流式细胞术检测HCT-8的凋亡率.结果 联合LY294002作用后,5-Fu、奥沙利铂对大肠癌细胞系HCT-8增殖的抑制作用明显增强(P<0.05),且能提高其凋亡率(P<0.05).结论 LY294002能有效提高化疗药物5-Fu、奥沙利铂体外对HCT-8细胞抑制作用的敏感性,抑制PI3K介导的信号转导通路,可明显提高大肠癌的化疗效果.     

恩度联合化疗对不同Stat6活化表型直结肠癌细胞的作用

目的研究恩度联合化疗对直结肠癌细胞的抑制作用,并进一步观察不同Stat6表型的直结肠癌细胞对恩度联合化疗药物敏感性的差异。方法采用MTT法检测不同浓度的恩度单药或联合5-Fu及奥沙利铂对2种不同Stat6活化表型的直结肠癌细胞(Caco-2和HT-29)的增殖抑制作用。用流式细胞仪检测不同药物处理组对2种直结肠癌细胞早期凋亡率的影响。结果恩度单药作用于Caco-2和HT-29细胞没有显示出明显的增殖抑制和凋亡促进的作用(P>0.05)。而恩度联合1种或2种化疗药物[(5-Fu)和奥沙利铂(OXP)]对这2种癌细胞的生长抑制和凋亡促进的能力明显升高(P<0.05和P<0.01)。恩度联合化疗药物对Caco-2细胞生长抑制率和早期凋亡率均高于HT-29细胞(P<0.05)。结论恩度联合化疗药物能更好的抑制直结肠癌细胞的增殖能力,不同Stat6活化状态可能成为评价化疗疗效的潜在指标之一。     

康艾注射液对胃癌细胞SGC-7901的抑制作用

目的探讨康艾注射液对胃癌细胞SGC-7901的抑制作用。方法胃癌细胞SGC-7901接受不同浓度康艾注射液,然后采用MTT法测定各组胃癌细胞SGC-7901的增殖情况,Boyden chamber侵袭小室测定各组胃癌细胞SGC-7901侵袭能力,划痕实验测定各组胃癌细胞SGC-7901迁移能力。结果康艾注射液对胃癌细胞SGC-7901增殖的抑制与药物浓度有关(P<0.05),浓度越大,抑制能力越强;康艾注射液对胃癌细胞SGC-7901侵袭、迁移的抑制与药物浓度有关(P<0.05),浓度越大,抑制能力越强。结论康艾注射液对胃癌细胞SGC-7901的增殖、侵袭、迁移均有抑制作用,且具有剂量依赖性。     

辣椒素联合DDP对宫颈癌HeLa229细胞增殖及侵袭力的影响

目的 探讨辣椒素联合DDP对宫颈癌HeLa229细胞增殖、耐药和侵袭力的影响.方法 将HeLa229细胞分为对照组、辣椒素组、DDP组和联合用药组,MTT法检测72 h后细胞的增殖情况及辣椒紊联合应用不同浓度DDP对宫颈癌细胞增殖的影响.Boyden chamber体外侵袭实验检测辣椒素及联合DDP后细胞体外侵袭力的变化.结果 MTT实验表明,辣椒素与DDP联合应用可明显抑制HeLa229细胞的增殖.与单独使用辣椒素或DDP组相比,细胞存活率显著降低;对照组和辣椒素组细胞的存活率均随着DDP浓度的增加而下降,但在同一浓度,辣椒素与DDP联合应用可明显提高HeLa229细胞对化疗药物的敏感性.体外侵袭实验结果表明,与单独使用辣椒素或DDP组相比,辣椒素与DDP联合应用使穿越Matrigel胶的细胞数明显减少.结论 辣椒素与DDP联合应用,可以抑制宫颈癌细胞的增殖和体外侵袭力,增强宫颈癌细胞对化疗药物的敏感性,因此辣椒素有望成为宫颈癌治疗中的辅助用药.     

SiHa细胞对化疗药物联合GIK液的敏感性研究

目的 研究宫颈癌SiHa细胞对GIK液联合化疗药物顺铂的体外敏感性.方法 采用MTT法测定宫颈癌SiHa细胞对3种不同浓度GIK液联合顺铂的体外敏感性.结果 不同浓度的GIK液联合顺铂对宫颈癌SiHa细胞的生长抑制作用比单独使用顺铂更强.结论 顺铂联合使用GIK液在体外对肿瘤细胞的抑制效果比单独使用顺铂更好,但不与GIK液浓度呈递增关系.     

全反式维甲酸对结肠癌不同增殖潜能细胞株增殖的抑制作用研究

目的:研究ATRA对结肠癌不同增殖能力细胞株生长抑制的可能机制,为ATRA应用于结肠癌的治疗提供可靠依据.方法:应用细胞观察、FACS和MTT方法,研究ATRA对结肠癌不同增殖能力细胞株LS174T和CW-2细胞的生长抑制现象.结果:LS174T的生长速度明显比CW-2细胞快.ATRA对体外培养的结肠癌细胞株LS174T和CW-2细胞的生长有明显抑制和诱导细胞分化作用.结论:ATRA对LS174T和CW-2细胞的生长有抑制作用,抑制细胞增殖的程度与ATRA的浓度有关,ATRA对结肠癌细胞有一定的抑制癌细胞增殖和诱导癌细胞分化作用.     

康莱特增加肺癌细胞对健择敏感性的实验研究

目的:研究康莱特联合化疗药物健择抑制人肺腺癌细胞95D生长的作用,同时寻找康莱特联合化疗药物健择作用的最佳时机。方法:采用MTT比色法进行检测。结果:康莱特单药对人肺腺癌95D的生长有抑制作用,联合健择的抑制率高于单药组;康莱特先于健择加入对95D的抑制最强。结论:康莱特体外对肺癌细胞有抗肿瘤和化疗增敏作用;康莱特先于健择加入对95D的抑制最强。     

康莱特增加肺癌细胞对健择敏感性的实验研究

目的：研究康莱特联合化疗药物健择抑制人肺腺癌细胞95D生长的作用,同时寻找康莱特联合化疗药物健择作用的最佳时机。方法：采用MTT比色法进行检测。结果：康莱特单药对人肺腺癌95D的生长有抑制作用,联合健择的抑制率高于单药组;康莱特先于健择加入对95D的抑制最强。结论：康莱特体外对肺癌细胞有抗肿瘤和化疗增敏作用;康莱特先于健择加入对95D的抑制最强。     

TRAIL联合化疗或热疗抑制人肝癌细胞SMMC-7721体外增殖作用的研究

目的:在国内外现有的研究基础上探讨数种化疗药物:顺铂、羟基喜树碱、丝裂霉素、健择或热疗联合肿瘤坏死因子相关凋亡诱导配体(tumornecrosisfac-tor-relatedapoptosis-inducingligand,TRAIL)体外抑制肝癌细胞增殖的效果,以确定联合方案是否具有协同效应。方法:使用MTT法测定单独或联合应用TRAIL及化疗药物羟基喜树碱、顺铂、丝裂霉素、健择或热疗对人肝癌SMMC-7721细胞的体外增殖的抑制作用,使用流式细胞仪检测不同方案对SMMC-7721细胞凋亡率的影响。结果:TRAIL联合应用4种化疗药物均可以显著提高化疗药物引起的细胞增殖抑制及细胞凋亡。以亚毒性剂量浓度的顺铂为例,对照组、化疗组、TRAIL组、TRAIL联合化疗组的细胞增殖抑制率分别为0、14·91%、17·92%和62·45%;细胞凋亡率分别为1·59%、3·38%、8·78%和27·58%。但TRAIL联合热疗并不表现出明显的协同作用。结论:联合应用TRAIL与化疗药物对SMMC-7721细胞体外增殖的抑制及诱导细胞凋亡具有显著的协同作用,联合应用TRAIL与热疗未表现出明显的协同作用。     

MTT法测定化疗药物及郑氏植物蛋白对肿瘤原代细胞体外增殖？…

目的与方法;为了给临床提供肿瘤标本细胞的生长信息并筛选敏感性抗癌药,提高疗效,本文以ＭＴＴ比色法对１００例实体瘤原代细胞进行了８种化部药物及郑氏植物蛋白对其体外增殖影响作用的测定。结果与结论：结果表明８和临床常用的化疗药物中以顺铂、卡铂、５－氟脲嘧啶、丝裂霉素Ｃ的抑瘤敏感性较高,但不同标本瘤细胞的敏感性药谱不一样,提示了肿瘤治疗个体化的必要性。同时显示郑氏植物蛋白对７０％的标本瘤细胞有促进增殖的作     

MARVELD1 interacting with catalase regulates reactive oxygen species metabolism and mediates the sensitivity to chemotherapeutic drugs in epithelial tumors of the reproductive system

Previous investigations have found that MARVEL domain‐containing 1 (MARVELD1) could inhibit tumor cell proliferation and enhance the sensitivity to chemotherapeutic drugs in hepatocellular carcinoma. Hence, it may be a valuable therapeutic target. In the study, we analyzed the responsive changes of MARVELD1 to 25 stress factors and expression of MARVELD1 in epithelial tumors of the reproductive system. We found that MARVELD1 was transferred to the cytoplasm and mitochondria under cell stress. And under cellular stress, the reactive oxygen species (ROS) levels decreased in MARVELD1 expressed cells while increased in the cells of MARVELD1‐specific siRNA treatment. Meanwhile, MARVELD1 overexpression significantly promoted the inhibition of tumor cell proliferation under cellular stress via affecting ROS metabolism, not cell cycle. In xenograft tumor tissues with MARVELD1 expression, the tumor growth was inhibited and accompanied by the lower ROS levels. Furthermore, we identified that MARVELD1 could interact with catalase (CAT) to enhance latter activity and maintain stability. And the enhanced sensitivity to chemotherapeutic drugs clearly depended on the ability of MARVELD1 scavenge the ROS in carcinoma cells of the reproductive system. Our findings clearly explain that MARVELD1 may regulate tumor cell proliferation and sensitivity to chemotherapeutic drugs via reducing the exorbitant ROS. The mechanism was that MARVELD1 interacted with CAT to maintain latter stability, and then ensure continuous ROS scavenge.     

粒─-巨细胞集落刺激因子对人胃腺癌TIL增殖及体外杀瘤活性的影响

本研究观察粒-巨细胞集落刺激因子（GM－CSF）对胃腺癌TIL增殖及体外杀瘤活性的影响。结果发现，单独GM－CSF刺激不诱导TIL增殖扩增，而在400U／ml的IL－2培养条件下，各剂量GM－CSF均可促进TIL增殖，其中，100μg／mlGM－CSF协同IL－2促增殖效应显著。体外杀瘤活性试验（MTT法）证实100ug／mlGM－CSF协同IL－2诱导TIL细胞增强了其杀瘤活性，无论是对同种异体细胞，亦或是自体肿瘤细胞。本文探讨了GM－CSF促TIL增殖及增强杀瘤活性的可能机制。     

Chemotherapy of human alpha-fetoprotein-producing gastric carcinomas grown in nude mice

We have examined the effects of chemotherapeutic drugs on tumor growth and metastasis of human alpha-fetoprotein-producing gastric carcinoma (AFPGC) xenografts growing in nude mice. These xenografts consisted of 3 hepatoid adenocarcinomas and 2 non-hepatoid, poorly differentiated adenocarcinomas. Mitomycin C and cisplatin inhibited the tumor growth and liver metastasis of hepatoid adenocarcinomas in nude mice. 5-fluorouracil also inhibited the growth of hepatoid adenocarcinomas but did not exhibit a significant antimetastatic action. Doxorubicin was effective only against non-hepatoid adenocarcinomas. These results indicate that chemotherapeutic drugs for AFPGC should be used according to the subtype of the tumor.     

Antitumor effects of IDN5109 on head and neck squamous cell carcinoma

Taxanes, a new class of antitumor drugs, are effective against a large number of human tumors, although there are problems with drug resistance. The novel taxane, IDN5109, is characterized by its high tolerability, antitumor efficacy, ability to overcome multidrug resistance, and oral bioavailabilty. We investigated the cellular response of IDN5109 to head and neck squamous cell carcinoma (HNSCC), and compared the antitumor activity of IDN5109 with that of paclitaxel. This is the first demonstration of antitumor effects of IDN5109 on HNSCC. In in vitro experiments, IDN5109 showed antiproliferative effects against HNSCC cell lines. After treatment with IDN5109, Bcl-2 and Bcl-XL were down-regulated, Bax was up-regulated, and caspase-3 was activated. After treatment with IDN5109, concentrations of both VEGF and IL-8 in the culture supernatant of HNSCC cells decreased. In in vivo experiments, the oral administration of IDN5109 showed antitumor effects against HNSCC tumor xenografts. Immunohistochemistry showed that IDN5109 inhibited tumor angiogenesis and induced apoptosis in HNSCC cells, producing a decreased blood vessel density and increased apoptosis index. On the basis of these results, IDN5109 is useful as a chemotherapeutic agent against HNSCC.     

Transfection of Smac sensitizes tumor cells to etoposide-induced apoptosis and eradicates established human hepatoma in vivo

A major concern in clinical treatment of cancers is resistance of tumors such as hepatocellular carcinoma (HCC) and osteosarcoma to current chemotherapy protocols. Here, we reported that overexpression of second mitochondria-derived activator of caspase (Smac) sensitized osteosarcoma cells and HCC cells in vitro to chemotherapeutic drugs-induced apoptosis. Constitutive expression of Smac resulted in enhanced Bax accumulation on mitochondria upon etoposide stimulation and inhibited Bcl-2-induced antiapoptosis activity. Thus, Smac would sensitize tumor cells to chemotherapeutic drugs in part through promoting Bax translocation to mitochondria and bypassing Bcl-2 block. Moreover, we demonstrated that blockade of Smac expression by antisense smac did not impair etoposide-induced apoptosis; however, p53-induced apoptosis was impaired in smac deficient Saos-2 cell. This suggested Smac might be required in p53-induced apoptosis. Most importantly, complete eradication of HepG2 xenografts in vivo was achieved upon combined therapy with Ad-Smac and 5-Fu. Thus, overexpression of Smac in tumor cells might be a potent strategy for cancer treatment by sensitization of tumor cells to chemotherapeutic drugs.     

Evaluation of drug efficacy in vitro using human small cell carcinoma of the lung spheroids

Five human small cell carcinoma of the lung (SCCL) cell lines selected from 25 established cultures were grown as three-dimensional spheroid tumor models in either spinner culture or in static, agar-coated multiwells. Volume doubling times for the cell lines were approximately 4.5 days. Decreases in spheroid volumes after exposure to a variety of chemotherapeutic agents were used as indicators of drug activity. To further quantify cell killing in SCCL spheroids by chemotherapeutic agents 24 hours after exposure to drugs, a technique was employed that measured maximum levels of incorporation of 125IUdR after continuous labeling for 48 hours. The results of the use of this assay report for SCCL spheroid responses to various concentrations of doxorubicin hydrochloride, cytosine arabinoside, mechlorethamine hydrochloride, cisplatin, or etoposide. Some evidence for an intertumor heterogeneous response to chemotherapy is presented for some of the drugs tested. This assay was also used to characterize a potentiated cell kill when etoposide is combined with cisplatin and to identify activity by a new compound, diazoacetylcholine iodide (DACI), which was synthesized as an agent targeted for SCCL cells.     

Usage of the NF-kappaB inhibitor sulfasalazine as sensitizing agent in combined chemotherapy of pancreatic cancer

Sulfasalazine is commonly used as an anti inflammatory agent and is known as a potent inhibitor of NF-kappaB. Some pancreatic carcinomas are characterized by a constitutively elevated NF-kappaB activity accounting for chemoresistance. To elucidate whether blockade of NF-kappaB activity with sulfasalazine is suitable for overcoming this chemoresistance in vivo, we employed a mouse model with subcutaneously xenotransplanted human Capan-1 pancreatic carcinoma cells. Fourteen days upon tumor inoculation, animals were randomized in 6 groups, receiving no treatment, treatment with gemcitabine or with etoposide, either alone or in combination with sulfasalazine, or with sulfasalazine alone. Two therapy regimens were given with a 7-day interval in between. Upon treatment with etoposide or gemcitabine alone, tumor sizes were moderately reduced to 65-68% and 50-65%, respectively, as compared to untreated tumors. Sulfasalazine alone only decreased temporarily the tumor sizes. Sulfasalazine in combination with gemcitabine showed only partially higher reduction in tumor sizes than gemcitabine alone, whereas the combination with etoposide reduced significantly the tumor sizes in all experiments (down to 20%). TUNEL-staining showed higher numbers of apoptotic cells in tumors from the combination groups, in particular with etoposide, and proliferation as indicated by Ki67 staining was strongly reduced. Furthermore, combined treatment of sulfasalazine with the cytostatic drugs led to a decreased blood vessel density. Immunohistochemical staining of the activated p65 subunit showed that sulfasalazine treatment abolished the basal NF-kappaB activity in tumor xenografts. These data imply that the well established anti-inflammatory drug sulfasalazine sensitizes pancreatic carcinoma cells to anti cancer drugs, in particular to etoposide in vivo by inhibition of NF-kappaB. This combined chemotherapy offers great potential for improved anti-tumor responses in pancreatic carcinomas.     

Anticancer drug distribution in lymph and blood during adjuvant chemotherapy after surgery for gastric carcinoma. A study with a combined preparation of 1-(2-tetrahydrofuryl)-5-fluorouracil and uracil

Previously the authors reported that the fat emulsion of 1-(2-tetrahydrofuryl)-5-fluorouracil, tegafur (FT-207), yielded significantly higher concentrations of tegafur in the lymph and plasma compared to tegafur enteric-coated granules (FT-G). However, the emulsification did not improve the metabolic conversion rate of tegafur to 5-fluorouracil (5-FU). A study was performed to assay the plasma and lymphatic concentrations of tegafur, 5-FU, and uracil in seven patients after radical surgery for gastric carcinoma who were given a combined oral preparation of FT-207 and uracil (UFT). Both lymph and plasma 5-FU levels after UFT were 20 times greater than those after FT-G, although FT-207 levels were not different. Patients given UFT showed significantly greater 5-FU and uracil concentrations in the lymph compared with the plasma. The results of this study suggest a potential use of UFT as an adjuvant postoperative chemotherapeutic agent for gastric carcinoma.     

缺氧导致胃癌化疗耐药的研究进展

胃癌是严重危害人类健康的恶性肿瘤，其化疗耐药问题日趋严重，导致胃癌治疗有效率下降。胃癌局部微环境的缺氧是导致胃癌化疗耐药的一个重要原因，由于肿瘤内血管结构和功能的异常以及肿瘤细胞的快速增殖引起肿瘤细胞氧耗增加，导致肿瘤组织局部缺氧，结果肿瘤细胞更具有侵袭性，容易发生远处转移，并且对化疗产生抵抗。本文从导致胃癌组织内缺氧的原因及缺氧微环境的特征、缺氧引起胃癌化疗耐药的现状及原因、改善缺氧导致的胃癌化疗耐药的措施等几个方面就缺氧导致胃癌化疗耐药的研究进展进行综述。