Objectives To explore the effects of curcumin and cisplatin on A549 lung cancer cell invasion and metastasis, and explore the influence of the two drugs on matrix metalloproteinase 9 (MMP-9) and E-cadherin protein. Methods MTT assay was performed to detect the effects of curcumin, cisplatin alone and the combination on A549 lung cancer cell proliferation. Transwell assay was performed to detect the effects of curcumin, cisplatin alone and the combination on the invasion and metastasis of lung cancer cells. Western blot was used to detect the protein expression of MMP-9 and E-cadherin. Results The proliferation inhibition of A549 lung cancer cell rate in 5, 10, 20, 40 μmol/L of curcumin was 6.50%±1.06%, 11.70%±0.88%, 22.97%±0.82%, 27.93%±0.94%, respectively. Compared with control group, the proliferation inhibition rates in four different curcumin groups were significantly increased (all P<0.01). The differences in the proliferation inhibition rates among four different curcumin groups were statistically significant (allP<0.05). The proliferation inhibition rates of A549 lung cancer cell in 1, 2, 4 mg/L of cisplatin were 7.12%±0.86%, 20.07%±1.14%, 26.88%±0.51%, respectively. Compared with control group, the proliferation inhibition rates in three different cisplatin groups were significantly increased (allP<0.01). The differences in the proliferation inhibition rates among three different cisplatin groups were statistically significant (allP<0.01). The proliferation inhibition rates of A549 lung cancer cell in curcumin (20 μmol/L) combined with cisplatin (1, 2, 4 mg/L respectively) were 28.37%±0.57%, 39.72%±0.64%, 46.27%±0.86%, respectively. Compared with control group and curcumin or cisplatin used alone, the proliferation inhibition rates of three combined groups were significantly increased (allP<0.01). The invasion inhibition rates of A549 lung cancer cell in curcumin group (20 μmol/L), cisplatin group (2 mg/L) and combined group (curcumin 20 μmol/L plus cisplatin 2 mg/L) were 38.62%±0.23%, 36.52%±0.33%, 63.78%±0.59%, respectively. Compared with control group and curcumin or cisplatin used alone, the invasion inhibition rates of combined group were significantly increased (allP<0.01). The protein grey values for curcumin group (20 μmol/L), cisplatin group (2 mg/L) and combined group (curcumin 20 μmol/L plus cisplatin 2 mg/L) were 0.768±0.047, 0.654±0.104, 0.684±0.008, 0.444±0.104 (MMP-9) and 0.603±0.170, 0.792±0.050, 0.784±0.045, 0.879±0.110 (E-cadherin), respectively. Compared with control group and curcumin or cisplatin used alone, the protein grey values of combined group were significantly different (allP<0.01 orP<0.05). Conclusions Curcumin and cisplatin combination can inhibit the invasion and metastasis of lung cancer A549 cells. Its mechanism may be related to downregulating MMP-9 and upregulating E-cadherin.
ObjectiveTo compare the recent efficiency and toxicity reactions of pemetrexed plus cisplatin and paclitaxel plus cisplatin for advanced lung adenocarcinoma. MethodsOne hundred and twenty-four patients with advanced lung adenocarcinoma treated in our hospital between January 2009 and December 2012 were divided into pemetrexed plus cisplatin group (group PP, n=63) and paclitaxel plus cisplatin group (group TP, n=61). The effect was evaluated after two courses of treatment, and the toxicity reactions were evaluated every course. ResultsThe objective response rate, disease control rate and progression-free survival in group PP and TP were respectively 58.7% vs 37.7%, 74.6% vs 52.5%, and 6.1 months vs 4.5 months, with significant differences (P<0.05). The incidence of nausea and vomiting, and white blood cell decrease (neutropenia) in group PP were significantly lower than that in group TP (χ2=16.164, P<0.001; χ2=9.469, P=0.002). There were no significant differences in incidence of thrombocytopenia, anemia and hepatic function damage (χ2=0.098, P=0.755; χ2=0.267, P=0.606; χ2=0.006, P=0.973). ConclusionPemetrexed plus cisplatin shows obviously superior effects and fewer side effects on advanced lung adenocarcinoma compared with paclitaxel plus cisplatin regime.
Lung cancer is the leading cause of cancer-related deaths worldwide. Despite the development and use of several targeting drugs for lung cancer therapy, the five-year survival rate has remained as low as 15% for the past three decades. Cisplatin-based chemotherapy is considered the first-line therapeutic strategy for lung cancer. However, developments of chemoresistance is a major obstacle for the successful treatment. Therefore, the development of novel therapy against cisplatin-resistance lung cancer is imperative. Photodynamic therapy (PDT), which is a non-invasive combinatorial therapeutic modality using light, photosensitizer (PS) and oxygen, may provide an unprecedented tool to develop more effective treatments. To provide experimental basis for its application in cisplatin-resistance lung cancer, we will discuss the biological effects of MPPa-photodynamic therapy in human cisplatin-resistance lung cancer cells in this article. Human cisplatin-resistance lung cancer cells A549/DDP were co-cultured with MPPa (0, 1, 2, 4, 8, 16 μmol/L) and exposed to light (0, 0.6, 1.2, 2.4, 3.6, 4.8 J/cm2), and cell viability was determined with CCK-8 assay. Flow cytometry was used to detect apoptosis, DCFH-DA staining was employed to observe reactive oxygen species (ROS), and Western blot was used to detect the expressions of B-cell lymphoma-2 (Bcl-2) protein and Bcl-2 associated X protein (Bax). The proliferation of A549/DDP cells was suppressed by PDT. The apop-totic rate in the PDT group was significantly higher than that in the control, MPPa or light group (P < 0.05). The level of ROS was increased. The expression of Bax was increased, and that of Bcl-2 was decreased. MPPa-photodynamic therapy can significantly suppress cell viability, and induce apoptosis in human cisplatin-resistance lung cancer cells.
Objective To systematically evaluate the clinical effectiveness and safety of raltitrexed plus cisplatin in the treatment of malignant pleural mesothelioma (MPM) when compared with other chemotherapy regimens. Methods We electronically searched PubMed, Embase, The Cochrane Library and Chinese Biomedicine Database to March, 2007. Randomized controlled trials (RCTs) and quasi-RCTs were identified, and Revman 4.2.10 was applied for statistical analyses. Results One RCT involving 250 patients was included, which compared raltitrexed plus cisplatin versus cisplatin alone in the treatment of MPM. In the intention-to-treat population, the median survival time was statistically longer in the raltitrexed plus cisplatin group as compared to cisplatin alone group. (11.4 versus 8.8 months, P=0.048). The incidence of grade 3/4 toxicities was similar between the two groups. Conclusion The current evidence available showed that, the combination of raltitrexed and cisplatin may prolong the survival time for MPM patients, with a low incidence of grade 3/4 toxicities. However, more high-quality RCTs are required to further define its clinical effectiveness.
Objective To observe the influence of cisplan on the expression of B7-H1 in retinoblastoma (RB) cells，and to investigate its mechanism. Methods Human RB cell line HXO-Rb44 cells were treated by 6 different concentrations of cisplan (0.000, 0.375, 0.750, 1.500, 3.000, 6.000 mu;g/ml), and their B7-H1 mRNA expression was determined by the reversetranscription polymerase chain reaction (RT-PCR) and fluorescence quantitative PCR (FQ-PCR); the B7-H1 protein expression was determined by immunofluorescence and flow cytometry. HXO-Rb44 cells were treated by 1.5 mu;g/ml cisplan for 0, 15, 30, 60, 120 min, then the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) was detected by Western blot.Results The expression of B7-H1 mRNA and protein in the 0.375, 0.750, 1.500, 3.000, 6.000 mu;g/ml group were significantly higher than that of the blank control group (F=395.478，112.03; P=0.000）. Western blot showed that cisplan (1.5 mu;g/ml) could activate ERK1/2 by increasing its phosphorylation in HXO-Rb44 cells. After cisplan treatment, the phosphorylation of ERK1/2 increased gradually and reached its peak at 30 min, and then went down gradually.Conclusion Cisplan can promote the expression of B7-H1 and activate ERK1/2 in RB cells.
ObjectiveTo evaluate the efficacy and toxicity of gemcitabine, paclitaxel plus cisplatin (GTP) chemotherapy for advanced urothelial carcinoma in China. MethodsTen patients with advanced urothelial carcinoma who underwent GTP chemotherapy regimens were collected from February to July 2014 in our hospital. According to solid tumor curative effect evaluation standard 1.1, we evaluated the clinical effcacy and collected the adverse reactions. ResultsTen patients with advanced urothelial carcinoma accepted first-line chemotherapy using GTP chemotherapy regimens. There was 1 case of complete remission, 4 cases of partial response, 3 stable cases, and 2 progressive cases. Adverse reactions of degree Ⅲ were mainly of hematology toxicity, including 5 cases of leukocytes and neutrophils reduction, and 1 case of anemia. The remaining adverse reactions included gastrointestinal reaction, hair loss, and abnormal renal function. ConclusionGTP chemotherapy regimen is a promising treatment for advanced urothelial carcinoma.
To study the effect of intraperitoneal hyperthermic double distiled water and cis-diamminedichloro-platinum(DDP) perfusion to the peritoneal cancerous ascites,intraperitoneal injection of H22 cancer cells (2×107 tumor cell,each mouse) were performed in LACA mice. Five days after cancer cells injection, intraperitoneal perfusion of simple hypertherrnic (43℃) double distiled water(group Ⅰ) isotonic fluid (group Ⅱ ). DDP (group Ⅲ ), and hypertherrnic double distiles water perfusion combined with DDP (guoup Ⅳ ) were performed .The results showed that cancer cells in the peritoneal cavity of LACA mice were seriously damaged, the production of ascites was markedly inhibited and the survival days of LACA mice were prolonged in all groups . .The intraperitoneal hyperthermic double distilled water perfusion with DDP group showed more effective result as compared with the other groups,Only 1 peritoneal implanted dissemination was found after treatment in this group,Basing on the experimental from September 1991 through September 1993,intraperitoneal hyperthermic double distiled water perfusion with DDP was used to treat 32 advanced gastric cancer patients after radical gastrectomy with satisfactory results.
Forty-six patients with advanced gastric cancer were investigated. 25 patients were randomized to receive intraperitoneal hyperthermic (43℃) hypotonic perfusion with high dose cis-diamminedichloroplatinum (60-200mg/m2 body surface) and sodium thiosulfate intraveneously (7.5g/m2 body surface). The time of the intraperotineal perfusion was 30 minutes with the total volume of the perfusate of 2500-3000ml. 21 patients were only operated. The sex ,age macro-or microscopic serosal invasion, and histologic type of two groups were similar and comparatible. We found no cancer cell in nine paients with positive intraperitoneal free cancer cell in the treated group. The postoperative 1-year survival rate of patients in the treated group (96.00%) was significantly higher than that of the random control group (48.54%), Ｐ＜0.01. The postoperative 1 1/2year survival rate in the treated group (68.88%) was also higher than that of the control group (40.00%), however, with no significant difference (Ｐ＞0.05). No serious myelosuppression, kindley,liver, and peripheral nerve damage, and other complications were found. The results indicated that this therapy is reasonably safe and could be a prophylactic theapy for the peritoneal recurrence after radical gastrectomy, which should be further investigated.
ObjectiveTo systematically review the efficacy and safety of intrapleural injection of endostar combined with cisplatin in treatment of non-small cell lung cancer (NSCLC) with malignant pleural effusion. MethodsDatabases including PubMed, The Cochrane Library (Issue 2, 2016), EMbase, Web of Science, CNKI, VIP and WanFang Data were searched to collect randomized controlled trials (RCTs) about endostar combined with cisplatin for NSCLC with malignant pleural effusion from inception to February 2016. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies. Then meta-analysis was performed by using RevMan 5.3 software. ResultsA total of 10 RCTs involving 610 patients were finally included. The results of meta-analysis showed that: The overall response rate and the improvement rate of quality of life in the endostar combined with cisplatin group were higher than that of the cisplatin alone group (RR=1.71, 95%CI 1.49 to 1.95, P<0.00001; RR=1.68, 95%CI 1.44 to 1.96, P<0.00001, respectively). However, There were no significant differences between two groups in incidence of gastrointestinal reaction, incidence of leucopenia and incidence of thrombocytopenia (all P values>0.05). ConclusionCompared with cisplatin, intrapleural injection of endostar combined with cisplatin can improve the overall response rate and improve the quality of life of NSCLC patients with malignant pleural effusion. Due to the limited quality and quantity of included studies, more high quality studies are needed to verify the above conclusion.
Non-small cell lung cancer (NSCLC) accounts for more than 80% of lung cancer. Nowadays, gemcitabine and cisplatin in combination have been adopted as the first-line chemotherapy for patients with NSCLC. This study aimed to monitor early response to combined chemotherapy of gemcitabine plus cisplatin in a mouse model of NSCLC by using 18F-fluorodeoxyglucose and 18F-fluorothymidine small animal positron emission tomography (PET). Lewis lung carcinoma-bearing C57BL/6 mice were treated with gemcitabine-cisplatin or saline. Small animal PET with 18F-FDG and 18F-FLT was performed before (baseline) and after treatment (on Day 3), respectively. Imaging results were confirmed by histopathological studies (hematoxylin and eosin staining, Ki67 staining). Compared to the results in the control group, gemcitabine-cisplatin in the treated group significantly inhibited tumor growth (P<0.05). In the treated group, the maximum standardized uptake value (SUVmax) of 18F-FLT decreased significantly from 0.59±0.05 (baseline) to 0.28±0.05 (Day 3) (P<0.05). There was no significant difference between baseline (4.35±0.46) and that on Day 3 (4.02±0.47) on 18F-FDG SUVmax (P>0.05). The proliferation of tumor assessed by Ki67 staining decreased significantly after treatment of one dose of gemicitabine-cisplatin (P<0.05). The staining of HE showed an increase in necrotic and inflam- matory cells after the treatment. This study demonstrated that the uptake of 18F-FLT reduced more rapidly and signi-ficantly than that of 18F-FDG and was less disturbed by the increase of inflammatory cells after chemotherapy.