Objective To dynamically study the formation of multidrug resistance(MDR) of human hepatocellular carcinoma cell SMMC-7721 induced by Adriamycin (ADM) and the role of multidrug resistance-associated protein(MRP) in its mechanisms.Methods Hepatocellular carcinoma cell SMMC-7721 was cultured in RPMI-1640 medium containing ADM with progressively increased concentration or directly cultured in medium containing different concentrations of ADM. Resistant index of drug-resistant variants of SMMC-7721 cell was determined by drawing cell dosage-reaction curves.Levels of MRP mRNA expression were detected by reverse transcription-polymerase chain reaction(RTPCR). Intracellular rubidomycin(DNR) concentration was examined by flow cytometry(FCM).Results With progressive increasing of ADM concentration in medium resistant index and levels of MRP mRNA expression were correspondingly increased but intracellular DNR concentration was markly reduced. When parental cells were directly cultured in medium containing different concentrations of ADM, the higher the ADM concentration, the higher the level of MRP mRNA expression, but intracellular DNR concentration was kept at the similar high level and most cells died. Conclusion ADM may progressively induce SMMC-7721 cell resistant to multiple chemotherapeutic drugs with reduced intracellular DNR accumulation associated with the overexpression of MRP gene.
目的:观察阿霉素持续静脉输注联合国产长春瑞滨(盖诺 NVB)治疗晚期乳腺癌的疗效及毒副反应,探讨治疗方式改变在化疗中的价值。方法:32例晚期乳腺癌患者,用NA方案:NVB 25 mg/m2 ivgtt d1,8、ADM 50 mg/ m2 civ 96h d1~4。每28天为一周期,至少2周期后评价疗效。观察疗效及毒副反应。结果:32例患者均随访。总共用药170周期,平均5.3周期。CR 5例,PR 18例,RR(CR+PR)71.9% 。初治、复治有效率分别为73.3%、70.6%,二者间无显著性差异(Pgt;0.05)。中位缓解期8.2个月。主要毒副反应为白细胞降低,发生率100%(32/32),32例中Ⅲ～Ⅳ度下降15例(46.9%);恶心、呕吐23例(71.9%),Ⅲ～Ⅳ度4例(12.5%);均发生脱发,Ⅲ～Ⅳ度5例(156%);口腔炎16例(50.0%),Ⅲ～Ⅳ度4例(12.5%);静脉炎2例(6.2%),均为Ⅰ度;心脏毒性发生3例(9.4%),为Ⅰ、Ⅱ度不等。无治疗相关性死亡。结论:阿霉素持续静脉输注与盖诺联合治疗晚期转移性乳腺癌疗效明确,毒副反应可以耐受,远期疗效值得进一步研究。
Objective To investigate the effects of adenovirus-mediated melanoma differentiation-associated gene-7 (mda-7)/IL-24 and/or adriamycin (ADM) on transplanted human hepatoma in nude mice and to explore a new way for hepatoma gene therapy combined with chemotherapy. Methods The recombinant adenovirus vector carrying Ad.mda-7 was constructed; Ad.mda-7 and/or ADM were injected into the tumor-bearing mice. Their effects on the growth of the tumor and the survival time of the mice were observed. The expressions of VEGF and TGF-β1 were detected by an immunohistochemistry method. Results Ad.mda-7 was constructed and expressed in vivo successfully. Compared with other three groups 〔control group (43.4±1.67) d, ADM group (64.2±4.14) d, Ad.mda-7 group (61.4±1.67) d〕, the mice treated with Ad.mda-7 combined with ADM had longer average survival time 〔(83.8±4.82) d, P＜0.01〕; the average size of tumor treated with Ad.mda-7 combined with ADM diminished significantly compared with that treated with ADM or Ad.mda-7 separately (P＜0.01). VEGF and TGF-β1 expressions of Ad.mda-7 group were (56.2±7.7)%, (35.2±4.5)%, respectively, and were lower than those in ADM group (VEGF: P＜0.05; TGF-β1: P＜0.01). VEGF expression of Ad.mda-7+ADM group was (37.3±5.0)%, and was significantly lower than that in other three groups (P＜0.01). TGF-β1 expression of Ad.mda-7+ADM group was (31.2±3.1)% and significantly lower than that in control group and ADM group (P＜0.01), however, there was no significant difference compared with Ad.mda-7 group (Pgt;0.05). Conclusion Ad.mda-7 combined with ADM has b antitumor potency and synergistic effects and suppresses the growth of human HCC xenograft in nude mice, possibly by inducing the apoptosis of hepatoma cell lines and suppressing tumor angiogenesis.
Objective To evaluate the effect of neoadjuvant chemotherapy on the expression of CXCR4 in breast cancer and its clinical significance.Methods The clinical data of 59 patients with breast cancer of stage Ⅱ and stage Ⅲ underwent neoadjuvant chemotherapy with paclitaxel plus epirubicin for 3 cycles between April 2005 and March 2009 were retrospectively analyzed. The expression of CXCR4 in the breast cancer tissues before and after neo-adjuvant chemotherapy was examined by immunohistochemistry and its relationship with clinicopathologic factors was analyzed.Results The CXCR4 positive expression was observed in 56 patients with breast cancer (94.9%), but not in corresponding nontumor normal tissues. The expression level of CXCR4 was correlated to lymph nodes metastasis (P=0.019) and breast cancer stage (P=0.040), but it was not correlated to age of patients, tumor size, grade, hormone receptor (ER and PR)， and HER2 status. The expression level of CXCR4 was significantly decreased after neoadjuvant chemotherapy. Decline extent of CXCR4 expression after chemotherapy and CXCR4 expression level were not correlated to the effect of neoadjuvant chemotherapy, while the effect of chemotherapy in patients expressed CXCR4 in cluster distribution was better than that in scattering distribution (P=0.015). Conclusion The decline extent of CXCR4 expression level after paclitaxel combined with epirubicin neoadjuvant chemotherapy is not correlated to the efficacy, but its expressing distribution may be considered as an index to the effect of neoadjuvant chemotherapy.
Objective To investigate the effect of the drug-resistance characteristic of neoplasm cell on the expression of Fas during the chemical medi-cure.Methods The adriamycin-resistance hepatic carcinoma cells (HepG2 cell lines) were estabilished by cell biology. Changes of expression of the HepG2 cell lines was determined by immunohistochemistry. Results When the HepG2 cell lines were not induced by adriamycin, the expression of Fas of them was weak and Fas mainly existed in cell membrane. When induced by adriamycin, the expression was enhanced and Fas mainly existed in cytochylema. Simultaneously, the death rate of the cell lines changed. The death rate of the drug-resistance cell lines in 0.1 μg/ml ADM was almost as same as that of non-drug-resistance cell lines without ADM (Ｐ＞0.05) and was significantly different from that of non-drug-resistance cell lines in 0.1 μg/ml ADM (Ｐ＜0.05). Conclusion Changes of the expression of Fas may be one of the drug-resistance mechanisms of carcinoma cell.
Objective To determine whether intravesically administered Adriamycin can prevent superficial bladder tumor to recur through assessing the efficacy of with intravesical Adriamycin and without intravesical Adriamycin after TURB-t. Method The search strategy was made according to the demand of Cochrane Collaboration. Medline, Embase，CBMdisc and the Cochrane Library were searched for RCTs. Data were extracted by two reviewers using the designed extraction form. RevMan were used for data management and analysis. Results Thirty three relevant trials were searched, of which eighteen trials were included and fifteen trials were excluded. Meta-analysis showed intravesically administered Pirarnbicin (THP), Epirubicin (EPI) and Adriamycin (ADM) can reduce the recurrence rate of superficial bladder cancer after operation during one or two years. Conclusions Intravesically administered THP, EPI and ADM can reduce the recurrence rate of superficial bladder cancer after TUPB-t’s operation during one or two years. In addition, the factors affecting the prognosis should be performed, such as the dosage of irrigation of bladder, reserving time and the course.
Objective To investigate the effects and mechanism of doxorubicin preconditioning in providing ischemic tolerance for rats abdomen island flaps. Methods Twenty-four healthy adult Sprague Dawley rats, 12 males and 12 females, were randomly divided into 3 groups (n=8): control group (group A), ischemic preconditioning group (group B), and doxorubicin preconditioning group (group C). After the abdomen island flap (6 cm × 3 cm in size) based on the superficial inferior epigastric neurovascular bundle was prepared, group A had no further treatment; group B was given a 10-minute ischemia followed by a 10-minute reperfusion for 4 times; and group C was given pretreatment with doxorubicin (1 mg/kg) by injection of the inferior epigastric vein. After 24 hours, the inferior epigastric vessels were blocked by vascular clamp for 4 hours, followed by reperfusion 2 hours to prepare ischemia/reperfusion (I/R) injury model. The rat survival was observed after operation; at 0, 8, 12, 24, and 30 hours after I/R injury, the malonyldiadehyde (MDA) and superoxide dismutase (SOD) levels were measured. At 7 days after I/R injury, the survival rate of flap were calculated and the flaps were harvested for histological observation. Results During experiment, 5 rats died (1 rat in groups A and B respectively, 3 rats in group C) and were added. The survival rates of the flap in group A (10.10% ± 0.43%) was lower than those in group B (91.63% ± 1.76%) and in group C (92.75% ± 1.48%) at 7 days after I/R injury, showing significant differences (P lt; 0.05), and there was no significant difference between groups B and C (t=0.29, P=0.77). Significant difference was found in MDA level and SOD level between group A and groups B, C after 8 hours (P lt; 0.05), and there was no significant difference between groups B and C (P gt; 0.05). Histological observation showed that inflammatory cells infiltration was more obvious and hyperplasia of fibers was weaker in group A than in groups B and C. Conclusion Doxorubicin preconditioning can provide ischemic tolerance for rats abdomen island flaps and protect flaps from the I/R injury. The possible mechanism may be related to that doxorubicin can induce endogenous protections.
【Abstract】ObjectiveTo establish adriamycin (ADM) resistant pancreatic cancer cell line SW1990/ADM and to investigate its drug resistance mechanism.MethodsADM-resistant pancreatic cancer cell line SW1990/ADM was obtained by culture of pancreatic cancer cell line SW1990 in vitro with intermittently increasing the concentration of ADM in the culture medium for ten months. After two months of drug free culture, its biological characteristics, drug sensitivity as well as the expression and function of multidrug resistant gene 1 (mdr1) were detected, respectively. ResultsCompared with the parental cell line, SW1990/ADM showed great changes in biological characteristics and developed a cross resistance to various chemotherapy drugs. The drug resistance indexes of cell line SW1990/ADM to ADM, mitomycin, fluorouracil and gemcitabine were 49.60, 7.25, 3.80 and 1.25, respectively. The level of mdr1 mRNA expression in cell line SW1990/ADM was much higher than that of the parental cell line（P＜0.01). ConclusionWe have established adriamycin resistant pancreatic cancer cell line SW1990/ADM with multidrug resistance phenotype, its multidrug resistance is positively relevant to the expression of mdr1.
【Abstract】ObjectiveTo compare the effects of newcastle disease virus (NDV) and adriamycin (ADM) on surface structure and actin of hepatocellular carcinoma cell lines SMMC-7721. Methods SMMC-7721 carcinoma cell lines were divided into 2 groups. NDV was added into one group, while ADM was added into the other group. The cells were then cultured at 5 time phases (8, 16, 24, 36 and 48 h). Intracellular actin and Ca2+ were examined by using immunofluorescence method. CD44 and intercellular adhesion molecule-1 (ICAM-1) were detected by using immunochemical method and flow cytometry, respectively. The change of cellular surface structure was observed by scan electron microscope. Results Cells gradually contracted and turned round over time. It was observed that actin was segmented and cells alignment became disordered. The mean fluorescence intensity of actin decreased in both groups, but it was obvious in NDV group. There were significant differences of fluorescence intensity between 2 groups at the phases of 16 h (P＜0.05), 24 h (P＜0.05), 36 h (P＜0.01) and 48 h (P＜0.05), except the one after 8 h. Intracellular Ca2+ concentration increased gradually in both groups, and the amplifications in NDV group were significantly higher at the phases of 24 h, 36 h and 48 h than those in ADM group (P＜0.01， P＜0.05 and P＜0.01, respectively). There were also differences at 8 and 16 h, but there were no statistical significance. The expression of CD44 in cells decreased. The mean fluorescence intensity of ICAM-1 raised gradually, and then came to peaking at 36 h, but there was no significant difference between two groups. All the above indices between different phases in the same group showed significant differences (P＜0.05). Conclusion Both NDV and ADM could make tumor cells degenerate and rupture, but the effect of NDV is more intensive. It could increase the fragility of cells and hasten the process of cell rupture. Disintegrated cancer cell and changes of adhesion molecule could lead cancer cells be identified, encapsulated, and killed by immune cells under static condition.