The interaction between cisplatin and erythrocyte membrane proteins was studied based on the quenching effect of cisplatin on the intrinsic fluorescence of proteins.A concentration-dependent quenching effect was obser...The interaction between cisplatin and erythrocyte membrane proteins was studied based on the quenching effect of cisplatin on the intrinsic fluorescence of proteins.A concentration-dependent quenching effect was observed.The presence of chloride and sulphate weakens the effect significantly.A pH-dependence was also noted with a stronger effect in acidic solution. The nature of the interaction is considered to be platinum-thiol group binding according to the effect of cisplatin on the fluorescence of FMA labeled membrane. The mechanism of the cisplatin-protein interactions was discussed based on the effect of coexisting anion展开更多
Recognition of DNA damage is a critical step for DNA damage-mediated cellular response. XPC is an important DNA damage recognition protein involved in nucleotide excision repair (NER). We have studied the XPC protein ...Recognition of DNA damage is a critical step for DNA damage-mediated cellular response. XPC is an important DNA damage recognition protein involved in nucleotide excision repair (NER). We have studied the XPC protein in cisplatin DNA damaging treatment-mediated cellular response. Comparison of the microarray data from both normal and XPCdefective human fibroblasts identified 861 XPC-responsive genes in the cisplatin treatment (with minimum fold change≥1.5).The cell cycle and cell proliferation-related genes are the most affected genes by the XPC defect in the treatment. Many other cellular function genes, especially the DNA repair and signal transduction-related genes, were also affected by the XPC defect in the treatment. To validate the microarray data, the transcription levels of some microarray-identified genes were also determined by an RT-PCR based real time PCR assay. The real time PCR results are consistent with the microarray data for most of the tested genes, indicating the reliability of the microarray data. To further validate the microarray data, the cisplatin treatment-mediated caspase-3 activation was also determined. The Western blot hybridization results indicate that the XPC defect greatly attenuates the cisplatin treatment-mediated Caspase-3 activation. We elucidated the role of p53 protein in the XPC protein DNA damage recognition-mediated signaling process. The XPC defect reduces the cisplatin treatment-mediated p53 response. These results suggest that the XPC protein plays an important role in the cisplatin treatment-mediated cellular response. It may also suggest a possible mechanism of cancer cell drug resistance.展开更多
Objective: The aim of our study was to explore the short-term effects and complication of interleukin-2 (IL-2) combining with Cisplatin in the treatment of malignant hydrothorax.Methods: Sixty-two cases patients with ...Objective: The aim of our study was to explore the short-term effects and complication of interleukin-2 (IL-2) combining with Cisplatin in the treatment of malignant hydrothorax.Methods: Sixty-two cases patients with malignant hydrothorax were randomly divided into two groups.Observation group was 31 examples,thoracic cavity injection IL-2 and Cisplatin;31 cases in control group using Cisplatin alone intra-thoracic injection.The regime of every week for 1–4 weeks was used to observe short term effects and complications.Results: The total response rate in observe group was higher than that in control group (90.3% vs.68.1%),which had statistically significant difference (P < 0.05).The complications included gastrointestinal tract reaction,bone marrow inhibition,chest pain and fever.The incidence rates of chest pain and fever in observe group was slightly higher than that in control group,but there was no statistically significant difference (P > 0.05).Conclusion: The IL-2 combining with Cisplatin intra-thoracic injection for malignant hydrothorax has the features of good therapeutic effects and slight poisonous side effects,which is worth to be used in clinic.展开更多
AIM： To determine the functional significance of TC21 in esophageal squamous cell carcinoma （ESCC）. METHODS： TC21 siRNA transfection was carried out using Hyperfectamine to knock down TC21, and tran- scripts were ...AIM： To determine the functional significance of TC21 in esophageal squamous cell carcinoma （ESCC）. METHODS： TC21 siRNA transfection was carried out using Hyperfectamine to knock down TC21, and tran- scripts were analyzed by reverse transcription-poly- merase chain reaction and protein by Western blotting.We demonstrated the effect of TC21 downregulation of cell signaling in esophageal cancer cells by assess- ing the phosphorylation status of its downstream tar- gets, phosphoinositide 3-kinase （PI3K）, phosphatase and tensin homolog （PTEN）, protein kinase B （pAl〈t）, nuclear factor-KB （NF-~B） and cyclinD1 using specific antibodies. Cell survival analysis after cisplatin treat- ment was carried out by cell viability assay and cell cycle analysis using flow cytometry. RESULTS： TC21 knockdown in human ESCC cell line TEl3 cells, showed only a marginal increase （14.2%） in cell death compared with control cells. The expres- sions of the signaling proteins PI3K and pAkt, transcrip- tion factor NF-KB, and cell cycle protein cyclin D1 were markedly decreased in response to TC21 downregula- tion, whereas the level of pPTEN, an antagonist of PI3K, was increased. In addition, we evaluated the potential of TC21 as a putative target for sensitizing ESCC cells to the chemotherapeutic agent cisplatin. Increased cell death （38.4%） was observed in cells treated with cis- platin after TC21 knockdown compared with cells which were treated with cisplatin alone （20% cell death）. CONCLUSION： Results suggest that TC21 mediates its effects via the PI3K-Akt pathway, NF-KB and cyclin D1, and enhances chemoresistance in esophageal cancer cells.展开更多
Objective： Irinotecan in combination with cisplatin for extensive-stage disease small-ceU lung cancer （ED-SCLC） patients has gained wide interest. Varying results for this treatment underpin the need for a synthesi...Objective： Irinotecan in combination with cisplatin for extensive-stage disease small-ceU lung cancer （ED-SCLC） patients has gained wide interest. Varying results for this treatment underpin the need for a synthesis of evidence. Methods： We conducted a literature-based meta-analysis to quantify the magnitude of the benefit comparing irinotecan in combination with cisplatin （IP） with etoposide in combination with cisplatin （EP） in ED-SCLC patients. The primary outcome was overall survival （OS） and progression-free survival （PFS）; secondary outcomes included overall response rate, 1- and 2-year survival rates, disease control rate and toxicity. Results： Four trials including 1,541 patients were identified in the analysis. No positive results （P〈0.05） were seen： OS （HR=0.85, CI95%=0.71-1.01; P=-0.08） with high heterogeneity （Chi2=7.76, dr=-3 [P=-0.05]; I2=61%）, PFS （HR=0.91, CI95%=0.74-1.28; P=-0.36） with high heterogeneity （Chi2=11.96, df=3 [P=-0.008]; I2=75%）, overall response rate（OR=1.16; CI95%=0.79-1.70; P=0.45）, disease control rate （OR=1.01; CI95%=0.74-1.38; P=0.95）, 1-year survival rate （OR = 1.30; CI95%=0.98-1.72; P=0.07） and 2-year survival rate （OR=1.97; CI95%=0.95-4.09; P=-0.07）. Fewer patients who received IP suffered severe hematologic toxicities （grade≥3）, such as neutropenia, thrombocytopenia and leucopenia. However, severe non-hematologic toxicities （grade≥3）, such as diarrhea, nausea, vomiting, fatigue, anorexia, and dehydration, were more common among patients who received IP. Conclusion： IP does not lengthen the overall survival or progression-free survival compared with EP in patients with ED-SCLC Fewer patients receiving IP had grade ≥ 3 hematological toxicities of nentropenia, leucopenia and thrombocytopenia, but more had grade≥3 diarrhea, nausea, vomiting, fatigue, anorexia and dehydration.展开更多
Objective: The aim of the study was to investigate the effect of Casticin (CAS) combination with Cisplatin (DDP) in sub-toxic concentration on apoptosis of human ovarian cancer HO-8910 cells in vitro and unravel the a...Objective: The aim of the study was to investigate the effect of Casticin (CAS) combination with Cisplatin (DDP) in sub-toxic concentration on apoptosis of human ovarian cancer HO-8910 cells in vitro and unravel the associated mechanisms. Methods: Human ovarian cancer HO-8910 cells were cultured in vitro. The inhibitory effect of CAS combination with DDP in sub-toxic concentration on viability of human ovarian cancer HO-8910 cells was evaluated by the MTT assay. Morphological changes of cell apoptosis were detected by Hoechst 33258 staining assay. Cell apoptosis rate was analyzed by flow cytometry. The protein expression level was analyzed by Western blot. Results: CAS in sub-toxic concentration and DDP in sub-toxic concentration could slightly inhibit Human ovarian cancer HO-8910 cells, but CAS combination with DDP in sub-toxic concentration significantly inhibited the growth of HO-8910 cells, and growth inhibition rate was increased drastically compared with the control group (P﹤0.01), and the inhibiting effect showed synergistic action. Human ovarian cancer HO-8910 cells showed the typical morphological changes of apoptosis and apoptosis rate markedly increased when they were exposed to CAS combination with DDP in sub-toxic concentration for 48 h. Western blot showed that the expression of bcl-2 protein was down-regulated and protein level of caspase-3 was activated by CAS combination with DDP in sub-toxic concentration. Conclusion: CAS combination with DDP in sub-toxic concentration could inhibit the cells growth and lead to cell apoptosis in human ovarian cancer HO-8910 cells. And the down-regulation of bcl-2 protein expression and activation of caspase-3 protein might contribute to CAS combination with DDP in sub-toxic concentration in human cancer HO-8910 cells.展开更多
Objective： The aim of this study was to study the cisplatin sensitizing effect and mechanism of anti-HPV16 E6- ribozyme on cervical carcinoma cell line. Methods： The anti-HPV16E6-ribozyme and empty eucaryotic expres...Objective： The aim of this study was to study the cisplatin sensitizing effect and mechanism of anti-HPV16 E6- ribozyme on cervical carcinoma cell line. Methods： The anti-HPV16E6-ribozyme and empty eucaryotic expressing plasmids were transfected into CaSKi cell, which named as CaSKi-R, CaSKi-P respectively. E6 mRNA, the sensitivity to cisplatin, apoptosis rates, expression of p53, Bcl-2, Bax and C-myc proteins and mRNA were examined by Northem blot, MTT colorimetric assay, PI/Annexin V stained methods, flow cytometry anslysis and RT-PCR, respectively. Results： E6 mRNA was less in CaSKi-R than in CaSKi. The sensitivity of CaSKi-R cells to cisplatin was 2.28 and 2.21 times than that of CaSKi and CaSKi-P cells. The apoptotic rates in CaSKi, CaSKi-P and CaSKi-R cells was （18.9 ± 3.5）%, （19.7 ± 4.8）% and （40.4 ± 4.5）%. The apoptotic rates was increased in CaSKi-R than that of CaSKi cells treated with cisplatin （P = 0.003）. Comapred with CaSKi cell, the expression of p53 （P = 0.000）, Bax protein （P = 0.002） was significantly higher and the expression of Bcl-2 protein （P = 0.005）, C-myc protein （P = 0.005） was significantly lower in CaSKi-R than that of CaSKi cell treated with cisplatin. Comapred with CaSKi cell, the expression of p53, Bax mRNA in CaSKi-R cell treated with cisplatin increased, while Bcl-2, C-myc mRNA decreased. Conclusion： CaSKi-R cells transfected by anti-HPVE6-ribozyme increased the sensitivity to cisplatin. The increase of sensitivity to cisplatin in CaSKi-R cells may be associated with increasing expression of p53, Bax protein, and decreasing expression of C-myc, Bcl-2 proteins.展开更多
Objective： The aim of this study was to observe the efficacy of gemcitabine combined with cisplatin （GP） in advanced non-smaU cell lung cancer （NSCLC） patients with low expression of ribonucleotide reductase 1 （...Objective： The aim of this study was to observe the efficacy of gemcitabine combined with cisplatin （GP） in advanced non-smaU cell lung cancer （NSCLC） patients with low expression of ribonucleotide reductase 1 （RRM1） protein using immunohistochemistry. Methods： RRM1 protein expression in tumor tissue was detected by streptavidin-peroxidase （SP） method of immunohistochemistry. GP regimen （gemcitabine 1000-1250 mg d1, d8, cisplatin 75 mg/m2） was given to advanced NSCLC patients with low expression of RRM1 protein. Results： In the total of 40 patients, these patients with RRM1 low expression performing GP chemotherapy had a good response rate, the objective response rate （ORR） was 47.5% （95% CI, 32.02%- 62.98%）, and the disease control rate （DCR） was 72.5% （95 % CI, 65.44%-79.56%）. ORR is 45.45% （5/11） in the squamous cell carcinoma patients while 48.15% （13/27） in the adenocarcinoma patients. Conclusion： Supedor ORR and DCR were found in advanced NSCLC patients with low expression of RRM1 protein expression performing GP regimen.展开更多
YSY01-A, as a novel proteasome inhibitor, has shown remarkable proliferation inhibitory effect on certain types of tumor cells. However, few studies have reported its effect on non-small cell lung cancer （NSCLC）, an...YSY01-A, as a novel proteasome inhibitor, has shown remarkable proliferation inhibitory effect on certain types of tumor cells. However, few studies have reported its effect on non-small cell lung cancer （NSCLC）, and its underlying mechanism remains unknown. In our present study, we aimed to figure out the inhibitory effects as well as the mechanism of proteasome inhibitor YSY01-A against A549 cells both individually and in combination with cisplatin. A549 cell proliferation inhibition was assessed by SRB assay. Its related protein expression levels were determined by western blot assay. Moreover, the change of intracellular cisplatin accumulation was examined by ICP-MS assay. The results suggested that YSY01-A significantly （P〈0.001） inhibited the proliferation of A549 cells （IC50 was 36.2 nM for 72 h） in a concentration-dependent and time-dependent manner. Compared with the negative control group, YSY01-A （60 nM, 48 h） down-regulated PI3K/Akt pathway in A549 cells by increasing the expression level of PTEN （P〈0.01）, and decreasing the expression level of PI3K （P〈0.001） and p-Akt/Akt （P〈0.001）. When combined with cisplatin, YSY01-A of different concentrations （5, 10, 20 nM） could significantly increase the inhibition effects on A549 cells compared with the cisplatin alone treatment, showing a synergistic effect. At the same time, YSY01-A could remarkably block the cisplatin-induced down-regulation of hCTR1 in a concentration-dependent manner and increase cisplatin uptake from 2.01 to 2.47 fold （P〈0.001）. In conclusion, compound YSY01-A could significantly inhibit proliferation of NSCLC A549 cells, showing a strong synergistic effect when combined with cisplatin. Down-regulation of PI3K/Akt pathway might be the mechanism of inhibitory effect of YSY0 l-A, and the combination with cisplatin might increase the expression of CTR1 and intracellular cisplatin accumulation.展开更多
文摘The interaction between cisplatin and erythrocyte membrane proteins was studied based on the quenching effect of cisplatin on the intrinsic fluorescence of proteins.A concentration-dependent quenching effect was observed.The presence of chloride and sulphate weakens the effect significantly.A pH-dependence was also noted with a stronger effect in acidic solution. The nature of the interaction is considered to be platinum-thiol group binding according to the effect of cisplatin on the fluorescence of FMA labeled membrane. The mechanism of the cisplatin-protein interactions was discussed based on the effect of coexisting anion
文摘Recognition of DNA damage is a critical step for DNA damage-mediated cellular response. XPC is an important DNA damage recognition protein involved in nucleotide excision repair (NER). We have studied the XPC protein in cisplatin DNA damaging treatment-mediated cellular response. Comparison of the microarray data from both normal and XPCdefective human fibroblasts identified 861 XPC-responsive genes in the cisplatin treatment (with minimum fold change≥1.5).The cell cycle and cell proliferation-related genes are the most affected genes by the XPC defect in the treatment. Many other cellular function genes, especially the DNA repair and signal transduction-related genes, were also affected by the XPC defect in the treatment. To validate the microarray data, the transcription levels of some microarray-identified genes were also determined by an RT-PCR based real time PCR assay. The real time PCR results are consistent with the microarray data for most of the tested genes, indicating the reliability of the microarray data. To further validate the microarray data, the cisplatin treatment-mediated caspase-3 activation was also determined. The Western blot hybridization results indicate that the XPC defect greatly attenuates the cisplatin treatment-mediated Caspase-3 activation. We elucidated the role of p53 protein in the XPC protein DNA damage recognition-mediated signaling process. The XPC defect reduces the cisplatin treatment-mediated p53 response. These results suggest that the XPC protein plays an important role in the cisplatin treatment-mediated cellular response. It may also suggest a possible mechanism of cancer cell drug resistance.
文摘Objective: The aim of our study was to explore the short-term effects and complication of interleukin-2 (IL-2) combining with Cisplatin in the treatment of malignant hydrothorax.Methods: Sixty-two cases patients with malignant hydrothorax were randomly divided into two groups.Observation group was 31 examples,thoracic cavity injection IL-2 and Cisplatin;31 cases in control group using Cisplatin alone intra-thoracic injection.The regime of every week for 1–4 weeks was used to observe short term effects and complications.Results: The total response rate in observe group was higher than that in control group (90.3% vs.68.1%),which had statistically significant difference (P < 0.05).The complications included gastrointestinal tract reaction,bone marrow inhibition,chest pain and fever.The incidence rates of chest pain and fever in observe group was slightly higher than that in control group,but there was no statistically significant difference (P > 0.05).Conclusion: The IL-2 combining with Cisplatin intra-thoracic injection for malignant hydrothorax has the features of good therapeutic effects and slight poisonous side effects,which is worth to be used in clinic.
基金Supported by Department of Science and Technology,Government of India
文摘AIM： To determine the functional significance of TC21 in esophageal squamous cell carcinoma （ESCC）. METHODS： TC21 siRNA transfection was carried out using Hyperfectamine to knock down TC21, and tran- scripts were analyzed by reverse transcription-poly- merase chain reaction and protein by Western blotting.We demonstrated the effect of TC21 downregulation of cell signaling in esophageal cancer cells by assess- ing the phosphorylation status of its downstream tar- gets, phosphoinositide 3-kinase （PI3K）, phosphatase and tensin homolog （PTEN）, protein kinase B （pAl〈t）, nuclear factor-KB （NF-~B） and cyclinD1 using specific antibodies. Cell survival analysis after cisplatin treat- ment was carried out by cell viability assay and cell cycle analysis using flow cytometry. RESULTS： TC21 knockdown in human ESCC cell line TEl3 cells, showed only a marginal increase （14.2%） in cell death compared with control cells. The expres- sions of the signaling proteins PI3K and pAkt, transcrip- tion factor NF-KB, and cell cycle protein cyclin D1 were markedly decreased in response to TC21 downregula- tion, whereas the level of pPTEN, an antagonist of PI3K, was increased. In addition, we evaluated the potential of TC21 as a putative target for sensitizing ESCC cells to the chemotherapeutic agent cisplatin. Increased cell death （38.4%） was observed in cells treated with cis- platin after TC21 knockdown compared with cells which were treated with cisplatin alone （20% cell death）. CONCLUSION： Results suggest that TC21 mediates its effects via the PI3K-Akt pathway, NF-KB and cyclin D1, and enhances chemoresistance in esophageal cancer cells.
文摘Objective： Irinotecan in combination with cisplatin for extensive-stage disease small-ceU lung cancer （ED-SCLC） patients has gained wide interest. Varying results for this treatment underpin the need for a synthesis of evidence. Methods： We conducted a literature-based meta-analysis to quantify the magnitude of the benefit comparing irinotecan in combination with cisplatin （IP） with etoposide in combination with cisplatin （EP） in ED-SCLC patients. The primary outcome was overall survival （OS） and progression-free survival （PFS）; secondary outcomes included overall response rate, 1- and 2-year survival rates, disease control rate and toxicity. Results： Four trials including 1,541 patients were identified in the analysis. No positive results （P〈0.05） were seen： OS （HR=0.85, CI95%=0.71-1.01; P=-0.08） with high heterogeneity （Chi2=7.76, dr=-3 [P=-0.05]; I2=61%）, PFS （HR=0.91, CI95%=0.74-1.28; P=-0.36） with high heterogeneity （Chi2=11.96, df=3 [P=-0.008]; I2=75%）, overall response rate（OR=1.16; CI95%=0.79-1.70; P=0.45）, disease control rate （OR=1.01; CI95%=0.74-1.38; P=0.95）, 1-year survival rate （OR = 1.30; CI95%=0.98-1.72; P=0.07） and 2-year survival rate （OR=1.97; CI95%=0.95-4.09; P=-0.07）. Fewer patients who received IP suffered severe hematologic toxicities （grade≥3）, such as neutropenia, thrombocytopenia and leucopenia. However, severe non-hematologic toxicities （grade≥3）, such as diarrhea, nausea, vomiting, fatigue, anorexia, and dehydration, were more common among patients who received IP. Conclusion： IP does not lengthen the overall survival or progression-free survival compared with EP in patients with ED-SCLC Fewer patients receiving IP had grade ≥ 3 hematological toxicities of nentropenia, leucopenia and thrombocytopenia, but more had grade≥3 diarrhea, nausea, vomiting, fatigue, anorexia and dehydration.
基金Supported by a grant from the Hunan Provincial Education Department(No.2011.91.11C1109)
文摘Objective: The aim of the study was to investigate the effect of Casticin (CAS) combination with Cisplatin (DDP) in sub-toxic concentration on apoptosis of human ovarian cancer HO-8910 cells in vitro and unravel the associated mechanisms. Methods: Human ovarian cancer HO-8910 cells were cultured in vitro. The inhibitory effect of CAS combination with DDP in sub-toxic concentration on viability of human ovarian cancer HO-8910 cells was evaluated by the MTT assay. Morphological changes of cell apoptosis were detected by Hoechst 33258 staining assay. Cell apoptosis rate was analyzed by flow cytometry. The protein expression level was analyzed by Western blot. Results: CAS in sub-toxic concentration and DDP in sub-toxic concentration could slightly inhibit Human ovarian cancer HO-8910 cells, but CAS combination with DDP in sub-toxic concentration significantly inhibited the growth of HO-8910 cells, and growth inhibition rate was increased drastically compared with the control group (P﹤0.01), and the inhibiting effect showed synergistic action. Human ovarian cancer HO-8910 cells showed the typical morphological changes of apoptosis and apoptosis rate markedly increased when they were exposed to CAS combination with DDP in sub-toxic concentration for 48 h. Western blot showed that the expression of bcl-2 protein was down-regulated and protein level of caspase-3 was activated by CAS combination with DDP in sub-toxic concentration. Conclusion: CAS combination with DDP in sub-toxic concentration could inhibit the cells growth and lead to cell apoptosis in human ovarian cancer HO-8910 cells. And the down-regulation of bcl-2 protein expression and activation of caspase-3 protein might contribute to CAS combination with DDP in sub-toxic concentration in human cancer HO-8910 cells.
文摘Objective： The aim of this study was to study the cisplatin sensitizing effect and mechanism of anti-HPV16 E6- ribozyme on cervical carcinoma cell line. Methods： The anti-HPV16E6-ribozyme and empty eucaryotic expressing plasmids were transfected into CaSKi cell, which named as CaSKi-R, CaSKi-P respectively. E6 mRNA, the sensitivity to cisplatin, apoptosis rates, expression of p53, Bcl-2, Bax and C-myc proteins and mRNA were examined by Northem blot, MTT colorimetric assay, PI/Annexin V stained methods, flow cytometry anslysis and RT-PCR, respectively. Results： E6 mRNA was less in CaSKi-R than in CaSKi. The sensitivity of CaSKi-R cells to cisplatin was 2.28 and 2.21 times than that of CaSKi and CaSKi-P cells. The apoptotic rates in CaSKi, CaSKi-P and CaSKi-R cells was （18.9 ± 3.5）%, （19.7 ± 4.8）% and （40.4 ± 4.5）%. The apoptotic rates was increased in CaSKi-R than that of CaSKi cells treated with cisplatin （P = 0.003）. Comapred with CaSKi cell, the expression of p53 （P = 0.000）, Bax protein （P = 0.002） was significantly higher and the expression of Bcl-2 protein （P = 0.005）, C-myc protein （P = 0.005） was significantly lower in CaSKi-R than that of CaSKi cell treated with cisplatin. Comapred with CaSKi cell, the expression of p53, Bax mRNA in CaSKi-R cell treated with cisplatin increased, while Bcl-2, C-myc mRNA decreased. Conclusion： CaSKi-R cells transfected by anti-HPVE6-ribozyme increased the sensitivity to cisplatin. The increase of sensitivity to cisplatin in CaSKi-R cells may be associated with increasing expression of p53, Bax protein, and decreasing expression of C-myc, Bcl-2 proteins.
文摘Objective： The aim of this study was to observe the efficacy of gemcitabine combined with cisplatin （GP） in advanced non-smaU cell lung cancer （NSCLC） patients with low expression of ribonucleotide reductase 1 （RRM1） protein using immunohistochemistry. Methods： RRM1 protein expression in tumor tissue was detected by streptavidin-peroxidase （SP） method of immunohistochemistry. GP regimen （gemcitabine 1000-1250 mg d1, d8, cisplatin 75 mg/m2） was given to advanced NSCLC patients with low expression of RRM1 protein. Results： In the total of 40 patients, these patients with RRM1 low expression performing GP chemotherapy had a good response rate, the objective response rate （ORR） was 47.5% （95% CI, 32.02%- 62.98%）, and the disease control rate （DCR） was 72.5% （95 % CI, 65.44%-79.56%）. ORR is 45.45% （5/11） in the squamous cell carcinoma patients while 48.15% （13/27） in the adenocarcinoma patients. Conclusion： Supedor ORR and DCR were found in advanced NSCLC patients with low expression of RRM1 protein expression performing GP regimen.
基金Eleventh Five-Year Plan for National Science and Technology Major Project(Grant No.2009ZX0930010)National Science Foundation of China(Grant No.81172915)a grant from Major New Drug Research and Development Platform of Peking University(GrantNo.2009ZX09301010)
文摘YSY01-A, as a novel proteasome inhibitor, has shown remarkable proliferation inhibitory effect on certain types of tumor cells. However, few studies have reported its effect on non-small cell lung cancer （NSCLC）, and its underlying mechanism remains unknown. In our present study, we aimed to figure out the inhibitory effects as well as the mechanism of proteasome inhibitor YSY01-A against A549 cells both individually and in combination with cisplatin. A549 cell proliferation inhibition was assessed by SRB assay. Its related protein expression levels were determined by western blot assay. Moreover, the change of intracellular cisplatin accumulation was examined by ICP-MS assay. The results suggested that YSY01-A significantly （P〈0.001） inhibited the proliferation of A549 cells （IC50 was 36.2 nM for 72 h） in a concentration-dependent and time-dependent manner. Compared with the negative control group, YSY01-A （60 nM, 48 h） down-regulated PI3K/Akt pathway in A549 cells by increasing the expression level of PTEN （P〈0.01）, and decreasing the expression level of PI3K （P〈0.001） and p-Akt/Akt （P〈0.001）. When combined with cisplatin, YSY01-A of different concentrations （5, 10, 20 nM） could significantly increase the inhibition effects on A549 cells compared with the cisplatin alone treatment, showing a synergistic effect. At the same time, YSY01-A could remarkably block the cisplatin-induced down-regulation of hCTR1 in a concentration-dependent manner and increase cisplatin uptake from 2.01 to 2.47 fold （P〈0.001）. In conclusion, compound YSY01-A could significantly inhibit proliferation of NSCLC A549 cells, showing a strong synergistic effect when combined with cisplatin. Down-regulation of PI3K/Akt pathway might be the mechanism of inhibitory effect of YSY0 l-A, and the combination with cisplatin might increase the expression of CTR1 and intracellular cisplatin accumulation.
